Pediatric Rheumatology Research

Pediatric Rheumatology Research | CPCE

CPCE’s researchers aim to improve clinical care in understudied rheumatic conditions, such as juvenile arthritis and systemic lupus erythematosus, by addressing critical knowledge gaps. Ongoing studies strive to improve diagnosis and evaluation of disease activity, compare the effectiveness of treatment strategies, and investigate the psychosocial impact of chronic disease.

Epidemiology and Clinical Outcomes in Juvenile Arthritis and Spondyloarthritis

Evaluation of Sacroiliitis in Children with JSpA

Improving Psychosocial Outcomes for Youth with Lupus

Juvenile Arthritis and Other Rheumatologic Conditions Published Research


Epidemiology and Clinical Outcomes in Juvenile Arthritis and Spondyloarthritis

This area of CPCE’s juvenile arthritis research is focused on defining the clinical and imaging features of children with early Juvenile spondyloarthritis (JSpA), which is an umbrella term that includes several categories of juvenile idiopathic arthritis (JIA), such as psoriatic arthritis and enthesitis-related arthritis. JIA is the most common rheumatologic chronic condition in childhood, of which JSpA accounts for approximately 15 to 20 percent. JSpA classifies a heterogeneous group of children with varying degrees of enthesitis (inflammation where the tendons attach to bone) and peripheral and axial arthritis. JSpA may evolve into ankylosing spondylitis, a condition characterized by radiographic damage to the joints of the spine and lower back.

To address the knowledge gaps of this understudied condition, CPCE research efforts in this area are specifically directed to better defining the disease and developing treatment strategies for children that will directly improve both clinical and patient-reported outcomes. This body of work includes the first study to evaluate the use of ultrasonography for the evaluation of enthesitis in a cohort of children with JSpA. An accurate diagnosis of enthesitis has implications regarding JIA classification, which in turn influences treatment decisions and monitoring for extra-articular manifestations of disease. This study is the largest study of ultrasonography and enthesitis in JIA to date.

This research area also includes an international effort to develop a disease activity score for children with JSpA for use in both clinical practice and research; this score has been subsequently validated using a retrospective multicenter database. This disease activity score is an important metric as current JIA disease activity measures do not account for the unique features of JSpA that include enthesitis and axial arthritis.  Researchers have also created a large longitudinal database of children with JSpA, using data from five pediatric rheumatology practices, to evaluate the comparative effectiveness of treatment strategies for children with newly diagnosed JSpA.

See the Published Research

Funding: National Institutes of Health

Please contact Pamela Weiss, MD, MSCE, attending physician and clinical research director of CHOP’s Division of Rheumatology, for more information about this line of research.


Evaluation of Sacroiliitis in Children with JSpA

CPCE juvenile arthritis research also includes evaluation of imaging used for the diagnosis of sacroiliitis, or arthritis of the lower back. CPCE researchers have recently shown that gadolinium contrast is not necessary when performing MRI to evaluate for suspected inflammatory sacroiliitis. This result is groundbreaking, as contrast is commonly used in centers throughout the US to make this diagnosis. CPCE researchers have also shown that sacroiliitis is common at diagnosis of JSpA (~20 percent of children are affected) and is frequently asymptomatic. Children who have elevated c-reactive protein and are HLA-B27 positive have the highest probability of having sacroiliitis.

What’s Next: Work is planned or underway to evaluate imaging and serologic predictors of progression of arthritis in the lower back, the utility of serial imaging with radiographs versus MRI for assessing disease progression and the optimal timing of such imaging.  Efforts are also underway to evaluate and optimize the utility of NIH patient-reported outcome measures (PROMIS) in children with JIA.

Researchers in the CPCE are also actively collaborating with the Childhood Arthritis Rheumatology Research Alliance to evaluate the comparative effectiveness of three commonly used treatment algorithms for children with polyarticular JIA.

See the Published Research

Funding: Patient Centered Outcomes Research Institute

Please contact Pamela Weiss, MD, MSCE, attending physician and clinical research director of CHOP’s Division of Rheumatology, for more information about this line of research.


Improving Psychosocial Outcomes for Youth with Lupus

This research seeks to improve health outcomes for youth with systemic lupus erythematosus (SLE), an autoimmune condition that can have significant morbidity and mortality due to organ damage.

In the United States SLE affects approximately 300,000 people, 20 percent of which have onset in childhood. Many youth with SLE experience psychological distress, due to onset of the disease in adolescence and the ongoing burden of having a chronic life-threatening condition that requires lifelong medication and frequent healthcare. Additionally, SLE and its treatment often have lasting and distressing effects on appearance.

Impaired psychosocial health can negatively impact other aspects of health, such as SLE disease control, physical function, transition to adult care and healthcare utilization. Through investigation of the psychosocial impact of SLE and the development of interventions to enhance psychosocial health, this research aims to improve overall health for youth with SLE.

In this research, we have utilized primary data and administrative data analysis, and mixed methods designs to examine the impact of SLE on mental and social aspects of health. The goals are three-fold:

  1. to understand the impact of SLE on psychosocial aspects of health for youth with SLE
  2. to improve mental health care for youth with SLE
  3. to improve patient-oriented and overall outcomes for youth with SLE

We have focused on characterizing the prevalence of depression and anxiety in youth with SLE (and the SLE-like syndrome of mixed connective tissue disease), as well as associated risk factors, relationship to healthcare utilization, treatment rates and disparities in care. The research findings have established a high prevalence of depression and anxiety in one third of SLE youth, with depression occurring more frequently in non-white patients and suicidal ideation being significantly higher than in healthy peers.

Depression in youth with SLE was associated with increased disease activity and damage, as well as longer disease duration. However, the high depression and anxiety rates in youth with SLE were similar to age and sex-matched peers with type 1 diabetes mellitus. This suggests that the general burden of chronic disease may play a more central role in depression and anxiety than SLE-specific inflammation, but studies are needed to further determine the role of inflammation.

Despite prevalent depression and anxiety symptoms, mental health treatment rates for youth with SLE were poor and those with depression had less frequent primary care visits than those without. Mental health treatment rates were also lower for youth with SLE than their diabetic peers. Our work highlights the unmet and disparate mental health needs of pediatric patients with SLE, implicating an important role for pediatric rheumatology clinicians in improving access to mental health care.

What’s Next: Work is underway to further characterize the impact of depression and anxiety on important health outcomes for youth with SLE and to develop interventions to improve the identification and treatment of mental health problems, as well as to reduce disparities in care for affected youth. CPCE researchers are also collaborating with the Childhood Arthritis Rheumatology Research Alliance to achieve these goals.

See the Published Research

Funding: National Institute of Health, Lupus Foundation of America, Center for Pediatric Clinical Effectiveness at The Children’s Hospital of Philadelphia, University of Pennsylvania

Please contact Andrea Knight, MD, MSCE, attending physician at CHOP, for more information about this line of research.


Pediatric Rheumatology Published Research

Epidemiology and Clinical Outcomes in Juvenile Arthritis and Spondyloarthritis

Weiss PF, Klink AJ, Behrens EM, Sherry DD, Finkel TH, Feudtner C, Keren R. Enthesitis in an Inception Cohort of Enthesitis-related Arthritis. Arthritis Care & Research. 2011 Sep;63(9):1307-12.

DeWitt EM, Kimura Y, Beukleman T, Nigrovic PA, Onel K, Prahalad S, Schneider R, Stoll ML, Angeles-Han S, Milojevic D, Schickler K, Vehe RK, Weiss JE, Weiss PF, Ilowite NT, Wallace CA, Juvenile Idiopathic Arthritis Disease Specific Research Committee of the Children’s Arthritis and Rheumatology Research Alliance. Consensus Treatment Plans for New-Onset Systemic Juvenile Idiopathic Arthritis. Arthritis Care and Research. 2012 July;64(7):1001-1010.

Beukelman T, Ringold S, Davis T, DeWitt EM, Pelajo C, Weiss PF, Kimura Y, CARRA Registry Investigators. Disease-modifying Antirheumatic Drug Use in the Treatment of Juvenile Idiopathic Arthritis: A Cross-sectional Analysis of the CARRA Registry. J Rheumatol. 2012 Sep;39(9):1867-74.

Weiss PF, Beukelman T, Schanberg LE, Kimura Y, Colbert RA, for the CARRA Registry Investigators. Enthesitis-related Arthritis is Associated with Higher Pain Intensity and Poorer Health Status in Comparison with Other Categories of Juvenile Idiopathic Arthritis: The Childhood Arthritis and Rheumatology Research Alliance Registry. J Rheumatol. 2012 Dec;39(12): 2341-51.

Horton DB, Sherry DD, Baldassano RN, Weiss PF. Enthesitis is an Extraintestinal Manifestation of Pediatric Inflammatory Bowel Disease. Ann Paediatr Rheumatol. 2012 Jan;1(4): 214-221.

Ringold S, Weiss PF, Beukelman T, DeWitt EM, Ilowite NT, Kimura Y, Laxer RM, Lovell DJ, Nigrovic PA, Robinson AB, Vehe RK. 2013 Update of the 2011 American College of Rheumatology Recommendations for the Treatment of Juvenile Idiopathic Arthritis: Recommendations for the medical therapy of children with systemic juvenile idiopathic arthritis and tuberculosis screening among children receiving biologic medications. Arthritis Rheum. 2013 Oct;65(10):2499-512.

Weiss PF, Klink AJ, Faerber J, Feudtner C. The Pediatric Rheumatology Quality of Life Scale: Validation of the English version in a US cohort of juvenile idiopathic arthritis. Pediatr Rheumatol. 2013 Nov;11(1):43.

Weiss PF, Chauvin NA, Klink AJ, Localio R, Feudtner C, Jaramillo D, Colbert RA, Sherry DD, Keren R. Detection of Enthesitis in Children with Enthesitis-related Arthritis: Dolorimeter examination compared to ultrasonography. Arthritis Rheumatol. 2014 Jan;66(1):218-27.

Ringold S, Weiss PF, Colbert RA, DeWitt EM, Lee T, Onel K, Prahalad S, Schneider R, Shenoi S, Vehe RK, Kimura Y, Juvenile Idiopathic Arthritis Research Committee of the Children’s Arthritis and Rheumatology Research Alliance (CARRA). Childhood Arthritis and Rheumatology Research Alliance Consensus Treatment Plans for New-Onset Polyarticular Juvenile Idiopathic Arthritis. Arthritis Care Res. 2014 Jul:66(7):1063-72.

Weiss PF, Colbert RA, Xiao R, Feudtner C, Beukelman T, DeWitt EM, Pagnini I, Wright TB, Wallace CA. Development and Retrospective Validation of the Juvenile Spondyloarthritis Disease Activity Index. Arthritis Care Res. 2014 Dec;66(12):1775-82.

Chauvin NA, Ho-Fung V, Jaramillo D, Edgar C, Weiss PF. Ultrasound of the Joints and Entheses in Healthy Children. Pediatr Radiol. 2015 Aug;45(9):1344-54.

Evaluation of Sacroiliitis in Children with JSpA

Weiss PF, Xiao R, Biko DM, Johnson AM, Chauvin NA. Detection of Inflammatory Sacroiliitis in Children With Magnetic Resonance Imaging: Is gadolinium contrast enhancement necessary? Arthritis Rheumatol. 2015 May;67(8):2250-6.

Weiss PF, Xiao R, Biko DM, Chauvin NA. Sacroiliitis at Diagnosis of Juvenile Spondyloarthritis Assessed by Radiography, Magnetic Resonance Imaging, and Clinical Examination. Arthritis Care Res. 2015 Jul; Epub ahead of print.

Improving Psychosocial Outcomes for Youth with Lupus

Garrett JP, Fung I, Rupon J, Knight A, Mizesko M, Paessler M, Orange JS. Presentation of Hemophagocytic Lymphohistiocytosis Due to a Novel MUNC 13-4 Mutation Masked by Partial Therapeutic Immunosuppression. Pediatric Rheumatol. 2012 May;10(1):13.

Knight AM, Weiss PF, Morales KH, Keren R. National Trends in Pediatric Systemic Lupus Erythematosus Hospitalization in the United States: 2000-2009. J Rheumatol. 2014 Mar;41(3):539-46.

Knight A, Weiss P, Morales K, Gerdes M, Gutstein A, Vickery M, Keren R. Depression and Anxiety and Their Association with Healthcare Utilization in Pediatric Lupus and Mixed Connective Tissue Disease Patients: A cross-sectional study. Pediatr Rheuamotol. 2014 Sep;12:42.

Knight, A;  Weiss, P;  Morales, K; Gerdes, M;  Rearson, M;  Vickery, M;  Keren, R (2015). Identifying Differences in Risk Factors for Depression and Anxiety in Pediatric Chronic Disease: A matched cross-sectional study of youth with lupus/mixed connective tissue disease and their peers with diabetes. J Pediatr. 2015 Dec;167(6):1397-1403.e1.