Project Title: “GROW (Generating Rheumatologists through Outreach and Workforce Expansion): A Multistep Project Towards Evaluating and Addressing the Pediatric Rheumatology Workforce Shortage”
Lay Summary: Pediatric rheumatology is a field dedicated to treating children with diseases where the body’s immune system attacks itself. Examples include diseases such as lupus or juvenile idiopathic arthritis. There have been significant advances in treating children with rheumatic diseases and, as a result, fewer children are developing the sequelae from these diseases, like joint destruction or organ damage. Despite these advances and improving outcomes, there is a current shortage of pediatric rheumatologists that is projected to worsen. This project will study facilitators and barriers that influence a person’s decision to pursue pediatric rheumatology. We intend for these results to inform our next steps, which include development of a mentorship and sponsorship program. This research will help pediatric rheumatologists better understand how to get more individuals to join the field, conduct research, and provide treatment for patients with rheumatic disease.
Project Title: “Evaluation of a Tool to Enhance Training of the Physical Examination of the Temporomandibular Joint”
Lay Summary: Arthritis of the temporomandibular joint (TMJ) occurs in many juvenile idiopathic arthritis (JIA) patients. TMJ involvement in JIA can often be asymptomatic and difficult to detect. The effects of TMJ arthritis can have a severe impact on health-related quality of life that may persist into adulthood. Earlier detection and treatment should reduce joint damage and resulting facial deformity. Lack of standardization of the orofacial examination in JIA patients has made it difficult to study TMJ arthritis. Recently, a standardized orofacial physical examination protocol for JIA patients was published. We would like to study the impact of using this protocol and a video training tool to see if it improves pediatric rheumatology fellows’ knowledge of TMJ arthritis and orofacial physical examination. This has the potential to improve clinical care by increasing detection of TMJ involvement in JIA patients which would prompt early treatment and prevent long term joint damage and deformity.
Project Title: “Development of the Macrophage Activation Syndrome Collaborative”
Lay Summary: Hyperinflammation is the term often used to describe a type of life-threatening systemic inflammation that can occur due to genetic defects, infections, rheumatic diseases, cancers, etc. Understanding the factors driving hyperinflammation is critical for treating it properly, but these are difficult to appreciate in any given patient. Previously, levels of the inflammatory proteins “CXCL9” (a biomarker of Interferon-gamma, IFNg, activity) and “IL-18” to distinguish between different causes of hyperinflammation. In this proposal, we will develop a collaborative of five CARRA sites active in hyperinflammation research to collect the earliest samples and test how diagnostically useful IL-18 and CXCL9 are in a more “real-world” scenario. This project will build this collaborative and collect and store a diverse set of samples and clinical data. Long-term, we hope to establish processes that could be rolled out CARRA-wide and build the scientific and logistical foundations for treatment studies that target IL-18 and IFNg.
Project Title: “Reproductive Health Concerns in Pediatric Onset Rheumatic Diseases: Filling the Needs of Patients and Parents Through Provider Education”
Lay Summary: Reproductive health is an encompassing term used to describe many different topics including but not limited to pregnancy, contraception, sexual relations, infertility, puberty, and monthly periods. Children with rheumatic diseases and their parents have unique reproductive health concerns as it relates to their disease and medications. There has been very little research on this topic in terms of their concerns and how to address them. Patients and parents might ask their pediatric rheumatologists about this topic, but they do not have any resources or dedicated training in this area. This study aims to understand and address the concerns and knowledge gaps of these populations and create a handout to address the needs discovered.
Project Title: “Defining salivary gland inflammation in childhood Sjogren's syndrome”
Lay Summary: Sjögren’s syndrome is a rare systemic autoimmune disease in children and can manifest with vague or unusual symptoms, leading to delays in diagnosis. Through ongoing collaboration with the international childhood Sjögren’s syndrome workgroup, the CARRA childhood Sjögren’s syndrome workgroup has collected a cohort of 291 patients with a clinical diagnosis of childhood Sjögren’s syndrome to study its natural history. We propose that the current 2016 ACR/EULAR adult classification criteria may not capture the spectrum of disease manifestations in childhood Sjögren’s syndrome. Using this existing data and examining salivary gland biopsy slides, we will compare disease manifestations in childhood Sjögren’s syndrome that influence the likelihood of obtaining a biopsy, and examine the relationships between salivary gland biopsy findings and disease characteristics. We anticipate that these studies will improve the diagnosis of childhood Sjögren’s syndrome and aid future studies.
Project Title: “Implementation of Electronic Health Record Optimization Tools to Capture and Extract CARRA Data”
Lay Summary: Patients are eager to participate in research. However, most research endeavors collect data outside of regular clinical routines. We know that patient-reported outcomes, such as pain, physical function, and self-reported disease activity assessments are instrumental in caring for a patient and provide valuable data about how a child is doing. However, these important data are not seen or used by the provider, nor are used to make important decisions about a child’s care. This project will fix this disconnect by leveraging the electronic health record to deliver CARRA questionnaires seamless, safely, and securely through the electronic health record functionality at Duke Children’s Health Center and displayed during a clinic visit. These data can be used for both clinical care and research, and be easily extracted for use into the CARRA Registry. This will improve clinical workflows and lay the foundation for a data-in-once model for the CARRA Registry.
Project Title: “Establishing the CARRA Registry Research Network for SJIA-LD (CARE-NETS)”
Lay Summary: Over the past decade, children with systemic juvenile idiopathic arthritis have increasingly been found to have a life-threatening lung disease (SJIA-LD). However, the causes and best treatments for this deadly complication are unknown. This project will create a multicenter network focused on understanding this disorder, called the CARRA Registry Research Network for SJIA-LD (CARE-NETS). CARE-NETS will identify a cohort of at least 40 children with SJIA-LD for enrollment in the CARRA Registry. We will develop short data forms to collect clinical information on lung disease, and collect biosamples over time. Finally, we will use these biosamples to perform immune cell phenotyping studies on SJIA-LD patients. Together, this pilot study will launch the first research network that will collect clinical data and serial biosamples from children with SJIA-LD through the CARRA Registry. CARE-NETS is an essential first step to further focused research through CARRA to find the cause of SJIA-LD.
Project Title: “Feasibility of conducting transcriptomic analyses in B cell subsets of pediatric lupus patients”
Lay Summary: Systemic lupus erythematosus is a chronic, multi-organ, autoimmune disease that typically affects young women of child-bearing age, and can be more severe and debilitating when diagnosed in childhood. To date, it is difficult to diagnose early in disease course and its treatment can be difficult, without good measures of response to therapy. To date, our group has demonstrated differences in the function of the genomes of children with lupus compared to healthy children. We propose to investigate how these differences affect the genes expressed in lupus patients that are not expressed in healthy children. Having this information will provide us with clues to how disease develops and how individual patients may respond to treatment.
Project Title: “Pilot Study for the Implementation of the CARRA Uveitis CTPs”
Lay Summary: Uveitis is a frequent complication of juvenile idiopathic arthritis (JIA) and can lead to permanent visual impairment. There is currently no standard approach to the treatment of uveitis. Recently, the CARRA uveitis subcommittee developed consensus treatment plans (CTPs) for two different scenarios in the treatment of JIA-associated uveitis. As with other CTPs, the intention of these plans, which each offer multiple options for therapy, is to streamline care in a way that allows for efficient collection of data using the CARRA registry. The ultimate goal is to be able to compare outcomes between treatment arms for both plans. We propose here a pilot study of the implementation of these CTPs at 9 CARRA sites to better understand the practical aspects of patient enrollment and data collection.
Project Title: “Identifying Research Priorities among Patients and Families of Children with Rheumatic Diseases Living in the United States"
Project Title: “Initial Results from a Pilot Comparative Effectiveness Study of 3 Methotrexate-based Consensus Treatment Plans for Juvenile Localized Scleroderma"
Project Title: “Prioritized Agenda for Mental Health Research in Pediatric Rheumatology from the Childhood Arthritis and Rheumatology Research Alliance Mental Health Workgroup"
Project Title: “Patient and Physician Discordance of Global Disease Assessment in Juvenile Dermatomyositis: Findings from the Childhood Arthritis & Rheumatology Research Alliance Legacy Registry”
Project Title: “sJIA with Lung Disease"
Lay Summary: In a subset of children with sJIA, a new form of lung disease is being detected as a serious complication. It seems most likely that this is a new and increasing problem, rather than better detection of a long-standing rare complication. Our recent work identified strong candidate risk factors for this new disease, which, if confirmed, will impact clinical management of children with sJIA. We have extended our study to analyze over 45 new cases of sJIA complicated by lung disease to confirm risk factors and possibly identify additional aspects of this disease. Data from the CARRA registry will be useful for comparing children with lung disease to a larger group of children with sJIA.
Project Title: “Uveitis treatment in CARRA II: TNF inhibitor and beyond"
Lay Summary: Uveitis, inflammation in the eyes, affects up to 20% of children with juvenile idiopathic arthritis (JIA) and may lead to vision loss if not treated appropriately. Disease modifying agents such as methotrexate and tumor necrosis factor inhibitors (TNFi) control disease in about 75% of children JIA-associated uveitis, but there is little literature to guide treatment of those in whom TNFi “fails.” In this pilot project we will identify current trends in post-TNFi treatment for uveitis in the CARRA II JIA Registry and provide an assessment of response to these treatments.
Project Title: “Validation of modified Juvenile Spondyloarthritis Disease Activity Index in Retrospective Cohorts"
Lay Summary: Juvenile Spondyloarthritis (JSpA) comprises the Juvenile Idiopathic Arthritis (JIA) ILAR categories of Enthesitis related arthritis (ERA), Psoriatic arthritis and Undifferentiated arthritis1. Patients with ERA are known to have higher pain intensity and poorer health status when compared to those with other JIA subtypes2. As such, accurate assessment of disease activity is important to target treatment and minimize sequelae of JSpA. Several features, such as enthesitis and sacroiliitis, are unique to this patient population. Conventional disease activity measures used in JIA such as the Juvenile Arthritis Disease Activity Score (JADAS) do not capture the unique features of this disease group. Several disease activity measures used in Ankylosing Spondylitis such as the BASDAI, BASFI, and ASDAS are also not appropriate because of less axial disease in the juvenile population3, 4. The Juvenile Spondyloarthritis Disease Activity Index (JSpADA Index) was developed by consensus as the first disease activity score for JSpA and was validated in a retrospective multicenter cohort of 243 children in 20145. The components of the JSpADAI include active joint count, active enthesitis count, pain, ESR or CRP, morning stiffness, clinical sacroiliitis, uveitis, and back mobility. The validity of this instrument has been tested in a single cohort of ERA patients from India6. Further, items comprising the index such as Schober’s, which is indicative of spinal involvement, has low relevance in the pediatric age group. This study is a validation of a modified JSpADA index, using prospectively collected retrospective data through the CARRA registry.
Project Title: “Prevalence of Paradoxical Psoriasis Secondary to TNF Inhibitor within CARRA Registry"
Lay Summary: Tumor necrosis factor inhibitors (TNFi) are commonly used to treat pediatric rheumatic diseases including juvenile idiopathic arthritis (JIA) and chronic recurrent multifocal osteomyelitis (CRMO). Psoriasis induced by TNF inhibition has been reported in these populations. However, the prevalence remains unknown and risk factors are unclear. This project aims to describe the prevalence of TNFi-associated psoriasis in patients with JIA and to better characterize the associated characteristics in this population using a large-scale data set from CARRA registry.