Spring 2019 Childhood Research Grants Announced
We recently granted $232,357 to childhood arthritis research. Grants are funded through the Childhood 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.
Rosemary Peterson, MD
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.
Nadine Saad, MD
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.
Tamara Tanner, MD
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.
Kaveh Ardalan, MD, MS
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.
Stephen Balevic, MD, MHS
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: In adolescence and early adulthood, rheumatology patients are required to become independent in managing their disease, health and well-being and navigating the health care system. Although health care providers recognize this as a crucial time to consistently monitor patients, there are still significant gaps in how health care empowers them to develop these skills. The purpose of this study is to learn about adolescents’ and young adults’ experiences transitioning from pediatric to adult rheumatology settings, and to obtain their concrete recommendations on how to improve upon this process. To do so, we will combine results from focus groups and a nationwide survey that asks participants questions about how they relate to and interpret the Six Core Elements of Healthcare Transition™, a model for improving transitional care in local health care settings. Our goal is to use these results to deliver more developmentally-tailored, patient-centered care to this at-risk population.
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: Psoriasis is an inflammatory skin disease that can be associated with joint inflammation (arthritis). Childhood psoriasis is frequently more severe when compared to adult-onset disease. Studies in adults suggest that psoriasis is caused by activated immune cells that cause damage. However, disease mechanisms, treatment response and outcomes are largely unstudied in children. The involvement of immune cells in psoriasis has been established. Determining types and numbers of immune cells may allow early diagnosis and the prediction of the development of arthritis. Patterns identified in this study may allow a personalized approach to treatment. Using modern, single-cell imaging technology, this study aims to investigate immune cells in controls and patients to understand disease mechanisms and deliver markers of individual outcomes, such as the development of arthritis. Understanding the composition and characteristics of immune cells in psoriasis will result in predictors of disease outcomes and new individualized treatments.
Mei-Sing Ong, PhD
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.
Kaila Schollaert-Fitch, MA
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: Linear scleroderma of the head is an uncommon autoimmune skin disease with significant medical and cosmetic impacts on children. Monitoring disease progression, defined as thinning of skin tissues, is difficult since accurate assessment requires significant clinical experience and hands-on time with patients. Noninvasive 3D cameras provide a finer assessment of skin changes, though stationary models are cumbersome and expensive. New handheld 3D cameras may potentially provide accurate monitoring of disease status across multiple clinical sites and providers, regardless of expertise. This pilot study will examine the feasibility and reliability of a low-cost, commercially available handheld 3D facial camera compared with an established clinic-based stationary 3D camera system, to accurately analyze and characterize pediatric scleroderma lesions. If this study is successful, handheld 3D cameras will give patients better access to scleroderma experts, eliminate unnecessary travel and provide an objective measure of skin changes to assist treatment decisions and clinical trials.
Emily Smitherman, MD
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.
Susan Thompson, PhD
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.
Rosemary Peterson, MD
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.
Nadine Saad, MDHospital 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.
Tamara Tanner, MDMontefiore 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.
Kaveh Ardalan, MD, MSAnn & 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.
Stephen Balevic, MD, MHSDuke 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/LUniversity 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: In adolescence and early adulthood, rheumatology patients are required to become independent in managing their disease, health and well-being and navigating the health care system. Although health care providers recognize this as a crucial time to consistently monitor patients, there are still significant gaps in how health care empowers them to develop these skills. The purpose of this study is to learn about adolescents’ and young adults’ experiences transitioning from pediatric to adult rheumatology settings, and to obtain their concrete recommendations on how to improve upon this process. To do so, we will combine results from focus groups and a nationwide survey that asks participants questions about how they relate to and interpret the Six Core Elements of Healthcare Transition™, a model for improving transitional care in local health care settings. Our goal is to use these results to deliver more developmentally-tailored, patient-centered care to this at-risk population.
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: Psoriasis is an inflammatory skin disease that can be associated with joint inflammation (arthritis). Childhood psoriasis is frequently more severe when compared to adult-onset disease. Studies in adults suggest that psoriasis is caused by activated immune cells that cause damage. However, disease mechanisms, treatment response and outcomes are largely unstudied in children. The involvement of immune cells in psoriasis has been established. Determining types and numbers of immune cells may allow early diagnosis and the prediction of the development of arthritis. Patterns identified in this study may allow a personalized approach to treatment. Using modern, single-cell imaging technology, this study aims to investigate immune cells in controls and patients to understand disease mechanisms and deliver markers of individual outcomes, such as the development of arthritis. Understanding the composition and characteristics of immune cells in psoriasis will result in predictors of disease outcomes and new individualized treatments.
Mei-Sing Ong, PhDHarvard 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.
Kaila Schollaert-Fitch, MAUniversity of Pittsburgh
Project Title: “Feasibility and Reliability of Handheld 3D Photogrammetry for Imaging Linear Scleroderma of the Head”
Award Amount: $25,000
Lay Summary: Linear scleroderma of the head is an uncommon autoimmune skin disease with significant medical and cosmetic impacts on children. Monitoring disease progression, defined as thinning of skin tissues, is difficult since accurate assessment requires significant clinical experience and hands-on time with patients. Noninvasive 3D cameras provide a finer assessment of skin changes, though stationary models are cumbersome and expensive. New handheld 3D cameras may potentially provide accurate monitoring of disease status across multiple clinical sites and providers, regardless of expertise. This pilot study will examine the feasibility and reliability of a low-cost, commercially available handheld 3D facial camera compared with an established clinic-based stationary 3D camera system, to accurately analyze and characterize pediatric scleroderma lesions. If this study is successful, handheld 3D cameras will give patients better access to scleroderma experts, eliminate unnecessary travel and provide an objective measure of skin changes to assist treatment decisions and clinical trials.
Emily Smitherman, MDUniversity 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.
Susan Thompson, PhDCincinnati 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.