Rotraud K. Saurenmann

The provisional Paediatric Rheumatology International Trials Organisation/American College of Rheumatology/european League Against Rheumatism Disease activity core set for the evaluation of response to therapy in juvenile dermatomyositis: A prospective validation study†‡

OBJECTIVE To validate a core set of outcome measures for the evaluation of response to treatment in patients with juvenile dermatomyositis (DM). METHODS In 2001, a preliminary consensus-derived core set for evaluating response to therapy in juvenile DM was established. In the present study, the core set was validated through an evidence-based, large-scale data collection that led to the enrollment of 294 patients from 36 countries. Consecutive patients with active disease were assessed at baseline and after 6 months. The validation procedures included assessment of feasibility, responsiveness, discriminant and construct ability, concordance in the evaluation of response to therapy between physicians and parents, redundancy, internal consistency, and ability to predict a therapeutic response. RESULTS The following clinical measures were found to be feasible, and to have good construct validity, discriminative ability, and internal consistency; furthermore, they were not redundant, proved responsive to clinically important changes in disease activity, and were associated strongly with treatment outcome and thus were included in the final core set: 1) physicians global assessment of disease activity, 2) muscle strength, 3) global disease activity measure, 4) parents global assessment of patients well-being, 5) functional ability, and 6) health-related quality of life. CONCLUSION The members of the Paediatric Rheumatology International Trials Organisation, with the endorsement of the American College of Rheumatology and the European League Against Rheumatism, propose a core set of criteria for the evaluation of response to therapy that is scientifically and clinically relevant and statistically validated. The core set will help standardize the conduct and reporting of clinical trials and assist practitioners in deciding whether a child with juvenile DM has responded adequately to therapy.

Risk factors for development of uveitis differ between girls and boys with juvenile idiopathic arthritis

OBJECTIVE Uveitis is the most common extraarticular manifestation of juvenile idiopathic arthritis (JIA) and is associated with considerable morbidity. The aim of this study was to examine the risk factors associated with uveitis in JIA. METHODS We conducted a chart review of 1,047 patients with JIA from a single tertiary care pediatric rheumatology center for factors associated with the development of uveitis. Special emphasis was put on the following known risk factors: oligoarthritis, antinuclear antibody (ANA) status, sex, and age at the time of onset of JIA. RESULTS The risk of uveitis developing was age dependent in girls but not in boys. Among girls, the risk was maximal (47%) in those who were ANA positive and were ages 1-2 years at the time of the onset of JIA; this risk decreased to <10% in those in whom the age at onset was >7 years. Only girls had an age-dependent and ANA-associated increased risk of uveitis. The time interval from the diagnosis of JIA to the diagnosis of uveitis was statistically significantly longer in patients in whom the onset of JIA occurred at a younger age (P = 0.04). This effect was even more pronounced in ANA-positive patients (P = 0.004). The JIA subtype did not influence a patients risk of the development of uveitis. CONCLUSION An age-associated risk of uveitis was observed only in girls who were younger than 7 years of age at the time of the onset of JIA. The duration of time between the diagnosis of JIA and the onset of uveitis was longer in patients in whom JIA was diagnosed at a younger age, especially in those who were ANA positive. We suggest that our findings have implications for uveitis screening in patients with JIA.

Temporomandibular joint involvement in children with juvenile idiopathic arthritis.

Objective. To determine the rate of temporomandibular joint (TMJ) involvement and find factors associated with TMJ arthritis in a single-center cohort of patients with juvenile idiopathic arthritis (JIA). Methods. Retrospective analysis of all patients with JIA visiting the rheumatology clinic between January 1, 2005, and December 31, 2006. Followup information was included until August 2008. A diagnosis of TMJ arthritis was based on clinical rheumatological and/or radiological findings. Results. After a mean followup time for JIA of 4.6 years (range 0.08–14.17), 86/223 patients (38.6%) had developed TMJ arthritis. The rate of TMJ involvement differed significantly among JIA subtypes (p = 0.0016), with 61% in extended oligoarticular, 52% in polyarticular rheumatoid factor (RF)-negative, 50% in psoriatic, 36% in systemic, 33% in polyarticular RF-positive, 33% in persistent oligoarticular, 30% in unclassified JIA, and 11% in enthesitis-related arthritis. The rate of TMJ involvement in our cohort was statistically significantly lower for patients who were HLA-B27-positive (p = 0.0002). In a multivariate analysis, the association of the following factors was confirmed: JIA subtype (p = 0.0001), a higher erythrocyte sedimentation rate (ESR) at diagnosis (p = 0.0038), involvement of joints of the upper extremity (p = 0.011), the absence of HLA-B27 (p = 0.023), and younger age at onset of JIA (p = 0.050). Conclusion. In our cohort of children with JIA, the overall rate of TMJ involvement was 38.6%. Patients with certain JIA subtypes, a higher ESR at disease onset, involvement of upper extremity joints, and younger age at diagnosis were more likely to develop TMJ arthritis. The presence of HLA-B27 seemed to be protective.

Course, complications, and outcome of juvenile arthritis–related uveitis

PURPOSE To describe the clinical features of uveitis in patients with juvenile idiopathic arthritis (JIA). METHODS Retrospective chart review of a subset of 1,081 consecutive JIA patients who were younger than 18 years of age and had uveitis, with a minimum of 1-year follow-up at a single center. RESULTS One hundred forty-two patients (13.1%) developed uveitis after a mean follow-up of 6.3 years (range, 0.10-23.2). Uveitis types were chronic anterior (97/142, 68.3%), acute anterior (23/142, 16.2%), recurrent anterior (17/142, 12%), and panuveitis (5/142, 3.5%). Uveitic complications were observed in 37.3% of cases (53/142) and 32.5% of eyes (74/228). When we compared uveitic eyes with complications to uveitic eyes without complications, we found the following significant differences: time interval from diagnosis of JIA to diagnosis of uveitis was shorter (mean, 1.3 years vs. 2.2 years; p = 0.003) and use of oral prednisone was greater (59.1% vs 15.6%; p < 0.0001) in the eyes with complications. Twenty-one children (21/142, 14.8%) with uveitis underwent a total of 62 ocular surgeries. Good visual acuity (20/40 or better) was found in 90.8% of eyes (159/175) and in both eyes of 87% of cases (94/108), impaired visual acuity in 6 eyes of 4 cases (6/175, 3.4%), and blindness in 10 eyes of 10 cases (10/175, 5.7%). Only 2 patients had reduced visual acuity in both eyes. Surgery was the single most important risk factor for reduced visual acuity at the last follow-up (p = 0.0086). CONCLUSIONS Most uveitic eyes with JIA achieved good visual outcome despite uveitic complications.

Association of the autoimmunity locus 4q27 with juvenile idiopathic arthritis

OBJECTIVE Juvenile idiopathic arthritis (JIA) is characterized by chronic arthritis and an autoimmune etiology. In several autoimmune diseases, including rheumatoid arthritis (RA), an association with the 4q27 locus has been reported. We undertook this study to investigate the possible role of the 4q27 locus in JIA. METHODS A case-control association study was conducted, with a total of 655 Caucasian JIA patients and 791 healthy controls divided into 2 independent sample sets. The rs6822844 marker in the 4q27 locus was genotyped. RESULTS In the first and larger sample set, a 5% decrease in T allele frequency was observed in patients compared with controls (allelic odds ratio [OR] 0.72 [95% confidence interval 0.55-0.95], P = 0.019), and in the second set, a 3% decrease was observed (allelic OR 0.81 [95% confidence interval 0.61-1.09], P = 0.169). The combined data set generated an OR of 0.76 (95% confidence interval 0.62-0.93, P = 7.08 x 10(-3)). When the different JIA subtypes were analyzed individually, significant decreases were seen in the subtypes with a polyarticular course of disease (extended oligoarthritis [P = 0.019] and rheumatoid factor-negative polyarthritis [P = 0.038]). CONCLUSION Our findings suggest that the 4q27 locus, previously reported to be associated with RA, type 1 diabetes mellitus, celiac disease, and psoriatic arthritis, is also associated with susceptibility to JIA.

Proposed Outcome Measures for Prospective Clinical Trials in Juvenile Idiopathic Arthritis- Associated Uveitis: A Consensus Effort From the Multinational Interdisciplinary Working Group for Uveitis in Childhood

To develop a set of core outcome measures for use in randomized controlled trials (RCTs) and longitudinal observational studies in juvenile idiopathic arthritis (JIA)–associated uveitis.

Contrast-enhanced MRI of the temporomandibular joint: findings in children without juvenile idiopathic arthritis:

Background Contrast-enhanced magnetic resonance imaging (MRI) is highly sensitive for assessing temporomandibular joint (TMJ) involvement in juvenile idiopathic arthritis (JIA), but only sparse data exist on normal TMJ appearance in children. Purpose To determine normal MRI appearance and enhancement pattern of pediatric TMJ as basis for diagnosing early arthritis. Material and Methods In 27 children (age range, 1.2–16.8 years) without TMJ pathology undergoing head MRI, fat-saturated T2-weighted (T2W) and postcontrast fat-saturated T1-weighted (T1W) images sagittally aligned to the 54 TMJs, besides standard T1W and T2W images, were assessed for bony and soft tissue signal intensity (SI), the amount of perceptible joint fluid, and contrast enhancement (CE). Results Bone marrow SI and CE of the mandible were consistent with varying degrees of residual red marrow in 96% of joints. The mandibular condyles were mostly isointense to the ramus, but in 9% showed mild edema-like bone marrow SI and CE. Small amounts of intraarticular fluid were detected in 31% on T2W images without fat saturation and in 83% on T2W images with fat saturation as fine lines in the upper or lower joint compartment or as small dots in an articular recess. Seventy-nine percent of all TMJs showed intense joint enhancement on early images restricted to areas of intraarticular fluid. Conclusion Small amounts of joint fluid with intense CE are a common MRI finding in TMJs of children without JIA and therefore should not be considered diagnostic for early arthritis.

Juvenile Psoriatic Arthritis (JPsA): juvenile arthritis with psoriasis?

BackgroundFollowing the introduction of the ILAR criteria for juvenile idiopathic arthritis, juvenile psoriatic arthritis (JPsA) has become a better recognized category within the inflammatory arthritides of childhood. There are fewer reports describing the characteristics and long-term outcome of patients with JPsA than other subtypes of JIA.The aim of our study was to determine the long-term outcome and clinical course of patients with juvenile psoriatic arthritis (JPsA) and to define subgroups of JPsA.MethodsClinical records of all patients meeting criteria for JPsA were reviewed and divided into 4 groups depending on their clinical features and onset type. Patient characteristics and clinical features at onset and during follow-up were determined.ResultsThe cohort consisted of 119 patients: 65 with oligoarticular-onset (55%; persistent 44 and extended 21), 34 (29%) with RF(-) and 4 (3%) RF(+) polyarticular and 16 (13%) enthesitis-related arthritis (ERA). At diagnosis patients with ERA were oldest and more commonly male (p=0.001 and =0.01 respectively). Patients with a polyarticular course had more involvement of small joints of the hands and wrist when compared to patients with persistent oligoarticular and ERA (p<0.001) while patients with ERA had more hip and sacroiliac arthritis (p<0.001 for both). Nail changes were seen in 66 patients (57%) and were associated with DIP involvement (p=0.0034).Outcome: Time to first inactive disease on, but not off, therapy was significantly longer among patients with polyarticular course when compared to oligoarticular and ERA (p=0.016 and p=0.48 respectively). Patients with polyarticular course more frequently had contractures during follow-up than other groups (p=0.01).ConclusionThe long-term outcome of with JPsA was generally good. Patients with JPsA did not appear to form distinct sub-group of patients but rather resembled JIA patients with onset types without psoriasis.

Clinical course and prognostic value of disease activity in the first two years in different subtypes of juvenile idiopathic arthritis

Juvenile idiopathic arthritis (JIA) is a heterogeneous disease involving chronic arthritis. The clinical course is characterized by a fluctuating pattern of active and inactive disease. We have described in detail the clinical course in different JIA subtypes during the first 2 years after diagnosis and studied its relationship to disease activity in the following years.

Comparison of patients with juvenile psoriatic arthritis and nonpsoriatic juvenile idiopathic arthritis: how different are they?

Objective. To compare the clinical features and outcome between patients with juvenile psoriatic arthritis (JPsA) and non-JPsA juvenile idiopathic arthritis (JIA). Methods. Fifty-three children with JPsA, 32 with < 5 joints in the first 6 months of disease (oligo–JPsA) and 21 (≥ 5 joints) polyarticular-onset (poly-JPsA) were compared to 53 patients with JIA who were matched by sex, age, date of diagnosis, and articular onset pattern. Results. There was no difference in the percentage of patients between the oligoarticular groups who developed extended oligoarthritis or in the percentage of patients who were positive for antinuclear antibodies. The only differences were that 25% of patients with oligo-JPsA had dactylitis compared to 0% of patients with oligo-JIA (p < 0.01) and 50% had nail pitting as compared to 18.7% (p < 0.05). In polyarticular patients the percentages with dactylitis were similar (19% vs 38%; p = 0.25). The frequency of uveitis was identical in the oligoarticular patients but a higher rate was seen in poly-JPsA compared to poly-JIA (23.8% vs 0%; p = 0.02), while contractures were more frequent in poly-JIA compared to poly-JPsA during the course of the illness (47.6% vs 14.3%; p = 0.03) but not at last followup (14.3% vs 4.7%; p = 0.6). At last followup the mean Childhood Health Assessment Questionnaire scores were similar in both the polyarticular and oligoarticular groups. Conclusion. There were only a few differences between patients with JPsA and JIA regarding disease onset, disease course, and outcome. We suggest that large, longterm prospective studies are required to accurately determine whether subdividing JIA according to psoriasis is worthwhile.