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Radiographic and Clinical Outcome in Early Juvenile Rheumatoid Arthritis and Juvenile Spondyloarthropathy: a 3-Year Prospective Study ANNE M

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Radiographic and Clinical Outcome in Early Juvenile Rheumatoid Arthritis and Juvenile Spondyloarthropathy: a 3-Year Prospective Study ANNE M Radiographic and Clinical Outcome in Early Juvenile Rheumatoid Arthritis and Juvenile Spondyloarthropathy: A 3-Year Prospective Study ANNE M. SELVAAG, BERIT FLATØ, KNUT DALE, GUNHILD LIEN, ODD VINJE, ANNA SMERDEL-RAMOYA, and ØYSTEIN FØRRE ABSTRACT. Objective. To describe radiographic findings at disease onset and 3-year followup in patients with juve- nile rheumatoid arthritis (JRA) and juvenile spondyloarthropathy (JSpA), to assess radiographic pro- gression and its predictors, and to prospectively assess clinical outcome and predictors of persistent dis- ease at 3-year followup. Methods. A total of 197 patients with JRA/JSpA were examined every 6 months for 3 years. Radiographic examination was performed at baseline and 3-year followup of knees and ankles (all patients) and of other joints on clinical indication. Remission was defined as minimum 6 months with- out medication and no clinical signs of active disease. Results. Radiographic abnormalities were found in 88% of the patients at onset and in 81% after 3 years. Frequency of swelling/osteoporosis decreased and frequency of abnormal growth increased from baseline to followup. Knees, hands, and wrists had most frequently radiographic abnormalities. Radiographic progression occurred in 38% of the patients. Joints with swelling/osteoporosis on radi- ographs, young age, and a large number of mobility-restricted joints at baseline were predictors of radi- ographic progression. At 3 years, 26% of the patients were in remission and 75% had been treated with disease-modifying antirheumatic drugs. Reduced well-being, a large number of active joints and nega- tive antinuclear antibody at baseline were predictors of persistent disease after 3 years. Conclusion. After 3 years most patients had radiographic abnormalities and persistent disease. Young age, many affected joints, reduced well-being, and negative antinuclear antibody at onset increased the risk of radiographic progression and persistent disease after 3 years. (First Release June 1 2006; J Rheumatol 2006;33:1382–91) Key Indexing Terms: JUVENILE RHEUMATOID ARTHRITIS JUVENILE SPONDYLOARTHROPATHY RADIOGRAPHY REMISSION PROGNOSIS RISK FACTORS Chronic arthritis in childhood often causes changes such as destruction may occur earlier5,6. Few studies have examined growth disturbances and destruction of bone in the joint area. prospectively the early radiographic changes in juvenile Radiographic documentation of the joint damage is an impor- rheumatoid arthritis (JRA) and juvenile spondyloarthropathy tant tool for the rheumatologist when assessing disease. (JSpA) in a systematic way. Radiographic progression has Studies have shown that about 25% of children with child- usually been measured by comparing frequencies of changes hood arthritis have radiographic damage after 6–10 years of at onset and at followup and not in terms of the progression of 1-3 disease duration . Radiographic erosions are known to be a changes in the individual patient. 1,4 late sign of severe arthritis , but some studies indicate that Several attempts have been made to establish and evaluate standardized radiographic assessment methods for children with juvenile arthritis6-13, but an internationally acceptable From the Department of Rheumatology, Rikshospitalet University Hospital, Oslo, Norway. radiographic assessment standard is not available. More stud- Supported by the Norwegian Foundation for Health and Rehabilitation ies using repeat standardized radiographs from representative through the Norwegian Rheumatism Association, the Norwegian Society patient cohorts with JRA/JSpA are needed to contribute to for Rheumatology, the Olga Imerslund Foundation, the Solveig Amalie standardization of radiographic readings for childhood arthri- Husbys Memorial Foundation, the Grethe Harbitz Legacy, and the Department of Rheumatology, Rikshospitalet University Hospital. tis. Predictors of erosions in JRA/JSpA have been found in 2,3,14 A.M. Selvaag, MD, Research Fellow; B. Flatø, MD, PhD, Senior longterm studies , but predictors of radiographic changes Consultant; K. Dale, MD, PhD, Professor; G. Lien, MD, PhD, Research in early disease course have not been explored prospectively. Fellow; O. Vinje, MD, PhD, Senior Consultant; A. Smerdel-Ramoya, MSc, Little is known about HLA genes and their association with PhD; Ø. Førre, MD, PhD, Professor. radiographic findings in childhood arthritis14. Address reprint requests to Dr. A.M. Selvaag, Department of Rheumatology, Rikshospitalet University Hospital, 0027 Oslo, Norway. Disease activity in juvenile arthritis may continue for many E-mail: [email protected] years, but may also remit with minor or no sequelae. Thirty to Accepted for publication February 26, 2006. sixty percent of children with arthritis are in remission after Personal non-commercial use only. The Journal of Rheumatology Copyright © 2006. All rights reserved. 1382 The Journal of Rheumatology 2006; 33:7 Downloaded on September 29, 2021 from www.jrheum.org 7–10 years of disease duration2,3,15. Some of the variations in positive. Positive IgM rheumatoid factor (RF) was defined as titer ≥ 64 by the Rose-Waaler test. HLA-B27 was determined by serologic testing24. HLA- these frequencies were due to the lack of established criteria DRB1 typing was performed using the nonisotopic method, based on poly- for remission. Recently, consensus was reached on prelimi- merase chain reaction (PCR) and hybridization with oligonucleotide probes nary criteria for remission in selected categories of juvenile labeled with biotin25. The HLA-DRB1 associations studied included DR1 idiopathic arthritis (JIA)16. Studies have shown that most (DRB1*01), DR4 (DRB1*04), DR5 (DRB*11 and *12), and DR8 remissions occur within 5 years after onset15,17, but few stud- (DRB1*08) alleles. HLA-DPB1 alleles were typed by sequence-specific oligonucleotide probing using a PCR, as described26. The HLA-DPB1 asso- ies have followed patients prospectively to assess remission ciations studied included DP2 (DPB1*02) and DP3 (DPB1*03) alleles. rates and predictors in early disease course. Predictors of per- 2,14 Radiographic examination. Radiographs from 174 patients were obtained by sistent disease after longterm followup have been reported , conventional technology with high resolution. In 23 patients a digital tech- but little is known about predictors of persistent disease early nique was used in accordance with the EULAR guidelines27. in the disease course18. The knees and ankles of all the patients were radiographed at baseline and The aim of our study was to: (1) prospectively describe the followup. Radiographic examination was done on clinical indication for other joints/joint groups. Contralateral joints were always included. The following radiographic findings in peripheral joints in early JRA/JSpA 8 joints/joint groups were studied: shoulders, elbows, wrists (radiocarpal at onset and after 3 years, (2) define radiographic progression joints and carpus), hands (interphalangeal and metacarpophalangeal joints), based on a standardized grading system for radiographic read- hips, knees, ankles, and feet (tarsal joints, metatarsophalangeal and interpha- ings and identify predictors of progression from among langeal joints). The radiographs of these joints were scored in chronological patient characteristics and measures of disease activity, and order by one of 2 trained radiologists (KD and VJ) not blinded to patient data, according to the Dale radiographic classification system for JRA: grade 0 (3) assess 3-year short-term clinical outcome and predictors of (normal joints), grade 1 (juxtaarticular osteoporosis and/or periarticular soft persistent disease at 3 years. tissue swelling), grade 2 (growth abnormality, bony erosion not present), grade 3 (growth abnormality and marginal bony erosions), grade 4 (deforma- MATERIALS AND METHODS tion and severe erosions), and grade 5 (gross destruction and deformity)9,28,29. Patients. Two hundred twenty-seven patients with JRA or JSpA and less than Interobserver error has been found to be low for this classification system9. 18 months of disease duration were admitted to the Department of An abnormal radiograph was defined as grade 1 or higher. Radiographic pro- Rheumatology, Rikshospitalet University Hospital, Oslo, between March gression was defined as an increase in the radiographic grade between base- 1995 and December 1999. Of these, 197 (87%) patients (61% girls) partici- line and followup, or from the first to the last radiograph taken during this pated in the study and were examined by a pediatric rheumatologist every 6 interval. An increase from grade 0 to ≥ 2, from grade 1 to ≥ 2, or from grade months for a mean ± SD of 3.2 ± 0.4 years. 2 to ≥ 3 was considered to be progression. An increase from grade 0 to 1 was Thirty (13%) of the 227 patients with JRA/JSpA did not participate. The not considered to be radiographic progression. parents of 18 of these children chose not to participate, 4 parents did not know Measures of physical function. The impact of arthritis on physical function Norwegian well enough, and 8 were excluded due to incomplete data. The was assessed by the Norwegian version of the Childhood Health Assessment participants were comparable to the nonparticipants with regard to age, sex, Questionnaire (CHAQ)30,31. The CHAQ is a disease-specific instrument that onset type, and disease duration (data not shown). measures physical disability and gives an index with values between 0 (no One hundred eighty-five of the patients had JRA according
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