Juvenile idiopathic arthritis (JIA) is the most commonly diagnosed rheumatic disease in childhood, affecting 1 to 4 per 1,000 children. Enthesitis-related arthritis (ERA) and psoriatic arthritis (PsA) account for approximately 20% and 10% of JIA, respectively. ERA and PsA are characterized by enthesitis of the lower extremities and arthritis of the axial and peripheral skeleton. Children with these 2 conditions are also at rik of developing sacroiliitis, or inflammation of the sacroiliac joints. Left untreated, sacroiliitis ay progress to spondylitis, a condition characterized by radiographic findings of squaring, erosions, syndesmophytes, diskitis, and fusion of the axial joints. In cross-sectional studies as many as 44% and 30% of children with ERA and PsA, respectively, have clinical or radiographic evidence of sacroiliitis. The prevalence of sacroiliitis in children with ERA and PsA at the time o diagnosis is unknown. Early identification and aggressive treatment of sacroiliitis may be an opportunity to alter the disease course. If pre-clinical sacroilitis is detectable at ERA/PsA onset then immediate treatment with anti-TNF agents may alter the course of sacroiliitis and greatly impact the function and quality of life of affected children and adolescents. The proposed research plan is designed to determine the prevalence of sacroiliitis, as defined by MRI, in children and adolescents with newly diagnosed ERA or PsA, and to assess the accuracy of physical examination and a history of inflammatory back pain for the detection of sacroiliitis in children and adolescents. The research proposed in this application will provide the candidate with preliminary data regarding the recruitment and enrollment of children in prospective patient- oriented research, and the implementation, conduct, and analysis of two inter-related ERA/PsA studies. The candidate anticipates this project will build the foundation to develop and support applications for additional R01 extramural funding to: 1) further investigate the diagnostic and predictive value of sacroiliitis at disease onset in clinical practice and trials of pediatric ERA nd PsA;2) investigate the role of whole body MRI at diagnosis for the detection of additional axial skeleton lesions in children with ERA or PsA at the time of diagnosis;and 3) perform prospective pharmacoepidemiology and comparative effectiveness studies for the treatment of sacroiliitis in pediatric ERA and PsA.

Public Health Relevance

New medications, including biologic agents, have revolutionized the treatment and improved the long-term outcomes of Juvenile Idiopathic Arthritis (JIA), including the 2 JIA categories of enthesitis-related arthritis (ERA) and psoriatic arthritis (PsA). The proposed research aims to identify children and adolescents with ERA and PsA who are risk of developing spinal inflammation, which causes long-term morbidity and dysfunction, and who may benefit from early treatment with these newer therapies. This research project will build the foundation to develop and support applications for additional extramural funding to for future intervention studies that will greatly impact the function and quality of life for children and adolescents with all forms of JIA.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Small Research Grants (R03)
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Special Emphasis Panel (ZAR1-EHB (M1))
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Witter, James
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Children's Hospital of Philadelphia
United States
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Manos, Cynthia K; Xiao, Rui; Brandon, Timothy G et al. (2017) Obesity and Pediatric Psoriatic Arthritis. Ann Paediatr Rheumatol 6:34-40
Weiss, Pamela F; Colbert, Robert A (2016) Reply. Arthritis Care Res (Hoboken) 68:1213-4
Weiss, Pamela F; Xiao, Rui; Biko, David M et al. (2016) Assessment of Sacroiliitis at Diagnosis of Juvenile Spondyloarthritis by Radiography, Magnetic Resonance Imaging, and Clinical Examination. Arthritis Care Res (Hoboken) 68:187-94
Weiss, Pamela F; Vossough, Arastoo; Chauvin, Nancy A (2016) Reply. Arthritis Rheumatol 68:263-4
Weiss, Pamela F; Xiao, Rui; Biko, David M et al. (2015) Detection of inflammatory sacroiliitis in children with magnetic resonance imaging: is gadolinium contrast enhancement necessary? Arthritis Rheumatol 67:2250-6
Gmuca, Sabrina; Weiss, Pamela F (2015) Evaluation and Treatment of Childhood Enthesitis-Related Arthritis. Curr Treatm Opt Rheumatol 1:350-364
Gmuca, Sabrina; Weiss, Pamela F (2015) Juvenile spondyloarthritis. Curr Opin Rheumatol 27:364-72
Weiss, Pamela F (2013) Evaluation and Treatment of Enthesitis-Related Arthritis. Curr Med Lit Rheumatol 32:33-41