Uncovering the hidden socioeconomic impact of juvenile idiopathic arthritis and paving the way for other rare childhood diseases: an international, cross-disciplinary, patient-centered approach (PAVE Consortium).

BACKGROUND: Juvenile idiopathic arthritis (JIA) refers to a heterogeneous group of rheumatic conditions in children. Novel drugs have greatly improved disease outcomes; however, outcomes are impacted by limited awareness of the importance of early diagnosis and adequate treatment, and by differences in access across health systems. As a result, patients with JIA continue to be at risk for short- and long-term morbidity, as well as impacts on virtually all aspects of life of the child and family. MAIN BODY: Literature on the socioeconomic burden of JIA is largely focused on healthcare costs, and the impact of JIA on patients, families, and communities is not well understood. High quality evidence on the impact of JIA is needed to ensure that patients are receiving necessary support, timely diagnostics, and adequate treatment, and to inform decision making and resource allocation. This commentary introduces the European Joint Programme on Rare Diseases: Producing an Arthritis Value Framework with Economic Evidence: Paving the Way for Rare Childhood Diseases (PAVE) project, which will co-develop a patient-informed value framework to measure the impact of JIA on individuals and on society. With a patient-centered approach, fundamental to PAVE is the involvement of three patient advocacy organizations from Canada, Israel, and Europe, as active research partners co-designing all project phases and ensuring robust patient and family engagement. The framework will build on the findings of projects from six countries: Canada, Germany, Switzerland, Spain, Israel, and Belgium, exploring costs, outcomes (health, well-being), and unmet needs (uveitis, mental health, equity). CONCLUSION: This unique international collaboration will combine evidence on costs (from family to societal), outcomes (clinical, patient and family outcomes), and unmet needs, to co-design and build a framework with patients and families to capture the full impact of JIA. The framework will support the development of high-quality evidence, encompassing economic and clinical considerations, unmet needs, and patient perspectives, to inform equitable resource allocation, health system planning, and quality of care better aligned with the needs of children with JIA, their families, and communities. Knowledge gained from this novel approach may pave the way forward to be applied more broadly to other rare childhood diseases.

A practical approach to uveitis screening in children with juvenile idiopathic arthritis.

BACKGROUND: Juvenile idiopathic arthritis (JIA)-associated uveitis typically presents as a silent chronic anterior uveitis and can lead to blindness. Adherence to current screening guidelines is hampered by complex protocols which rely on the knowledge of specific JIA characteristics. The Multinational Interdisciplinary Working Group for Uveitis in Childhood identified the need to simplify screening to enable local eye care professionals (ECPs), who carry the main burden, to screen children with JIA appropriately and with confidence. METHODS: A consensus meeting took place in January 2023 in Barcelona, Spain, with an expert panel of 10 paediatric rheumatologists and 5 ophthalmologists with expertise in paediatric uveitis. A summary of the current evidence for JIA screening was presented. A nominal group technique was used to reach consensus. RESULTS: The need for a practical but safe approach that allows early uveitis detection was identified by the panel. Three screening recommendations were proposed and approved by the voting members. They represent a standardised approach to JIA screening taking into account the patient's age at the onset of JIA to determine the screening interval until adulthood. CONCLUSION: By removing the need for the knowledge of JIA categories, antinuclear antibody positivity or treatment status, the recommendations can be more easily implemented by local ECP, where limited information is available. It would improve the standard of care on the local level significantly. The proposed protocol is less tailored to the individual than the 'gold standard' ones it references and does not aim to substitute those where they are being used with confidence.

New and Updated Recommendations for the Treatment of Juvenile Idiopathic Arthritis-Associated Uveitis and Idiopathic Chronic Anterior Uveitis.

OBJECTIVE: The Multinational Interdisciplinary Working Group for Uveitis in Childhood identified the need to update the current guidelines, and the objective here was to produce this document to guide clinicians managing children with juvenile idiopathic arthritis-associated uveitis (JIAU) and idiopathic chronic anterior uveitis (CAU). METHODS: The group analyzed the literature published between December 2014 and June 2020 after a systematic literature review conducted by 2 clinicians. Pediatric rheumatologists were paired with ophthalmologists to review the eligible 37 publications. The search criteria were selected to reflect those used for the 2018 Single Hub and Access point for pediatric Rheumatology in Europe (SHARE) recommendations, in order to provide an update, rather than a replacement for that publication. The summary of the current evidence for each SHARE recommendation was presented to the expert committee. These recommendations were then discussed and revised during a video consensus meeting on January 22, 2021, with 14 voting participants, using a nominal group technique to reach consensus. RESULTS: JIAU treatment was extended to include CAU. Fourteen recommendations regarding treatment of JIAU und CAU with >90% agreement were accepted. CONCLUSION: An update to the previous 2018 SHARE recommendations for the treatment of children with JIAU with the addition of CAU was created using an evidence-based consensus process. This guideline should help support clinicians to care for children and young people with CAU.

Discrete Choice Experiment on a Magnetic Resonance Imaging Scoring System for Temporomandibular Joints in Juvenile Idiopathic Arthritis.

OBJECTIVE: To determine the relative importance weights of items and grades of a newly developed additive outcome measure called the juvenile idiopathic arthritis (JIA) magnetic resonance imaging (MRI) scoring system for the temporomandibular joint (TMJ) (JAMRIS-TMJ). METHODS: An adaptive partial-profile, discrete choice experiment (DCE) survey using the 1000Minds platform was independently completed by members of an expert group consisting of radiologists and non-radiologist clinicians to determine the group-averaged relative weights for the JAMRIS-TMJ. Subsequently, an image-based vignette ranking exercise was done, during which experts individually rank ordered 14 patient vignettes for disease severity while blinded to the weights and unrestricted to JAMRIS-TMJ assessment criteria. Validity of the weighted JAMRIS-TMJ was tested by comparing the consensus-graded, DCE-weighted JAMRIS-TMJ score of the vignettes with their unrestricted image-based ranks provided by the experts. RESULTS: Nineteen experts completed the DCE survey, and 21 completed the vignette ranking exercise. Synovial thickening and joint enhancement showed higher weights per raw score compared to bone marrow items and effusion in the inflammatory domain, while erosions and condylar flattening showed nonlinear and higher weights compared to disk abnormalities in the damage domain. The weighted JAMRIS-TMJ score of the vignettes correlated highly with the ranks from the unrestricted comparison method, with median Spearman's ρ of 0.92 (interquartile range [IQR] 0.87-0.95) for the inflammation and 0.93 (IQR 0.90-0.94) for the damage domain. CONCLUSION: A DCE survey was used to quantify the importance weights of the items and grades of the JAMRIS-TMJ. The weighted score showed high convergent validity with an unrestricted, holistic vignette ranking method.

Magnetic Resonance Imaging Followup of Temporomandibular Joint Inflammation, Deformation, and Mandibular Growth in Juvenile Idiopathic Arthritis Patients Receiving Systemic Treatment.

OBJECTIVE: To investigate the course of temporomandibular joint (TMJ) inflammation, osseous deformation, and mandibular ramus growth in children with juvenile idiopathic arthritis (JIA) during systemic therapy. METHODS: Longitudinal study of 38 consecutive patients with JIA (29 female, median age 9.0 yrs, interquartile range 6.2-10.7 yrs) receiving systemic therapy with TMJ involvement, with 2 TMJ magnetic resonance imaging (MRI) examinations ≥ 2 years apart and no TMJ corticosteroid injection. Clinical and MRI findings were compared between initial and followup examinations and between TMJ with and without active inflammation at baseline. RESULTS: Over a median period of 3.6 years (range, 2.0-8.7 yrs), MRI grade of TMJ inflammation improved (p = 0.009) and overall osseous deformity tended to become less severe (p = 0.114). In TMJ with arthritis at baseline (46 TMJ), both the grades of inflammation (p < 0.001) and deformity (p = 0.011) improved. In TMJ with no arthritis at baseline (30 TMJ), the frequency and grade of condylar deformation remained stable. Mandibular ramus growth rates were not significantly different between TMJ with and without arthritis at baseline (1.3 mm/yr vs 1.5 mm/yr, p = 0.273), and were not correlated with the degree of inflammation at baseline or followup. The frequency of facial asymmetry tended to be lower at followup than at initial examination (24% vs 45%, p = 0.056). CONCLUSION: Our results suggest that systemic treatment of TMJ arthritis in children with JIA decreases the degree of inflammation seen on MRI, preserves osseous TMJ morphology, and maintains normal mandibular ramus growth.

Temporomandibular joint magnetic resonance imaging findings in adolescents with anterior disk displacement compared to those with juvenile idiopathic arthritis.

BACKGROUND: Deformation of the mandibular condyle can be associated with anterior disk displacement (ADD) or involvement of the temporomandibular joint (TMJ) by juvenile idiopathic arthritis (JIA). Diagnostic differentiation is critical for proper management. OBJECTIVES: To compare morphology and inflammation between TMJs with ADD and JIA. METHODS: Retrospective assessment of contrast-enhanced TMJ MRI in 18 adolescents (15 female, mean age 15.1 ± 1.9 years) with ADD and age- and gender-matched patients with JIA. Articular disk findings, inflammatory signs and osseous morphology were compared. RESULTS: In the ADD group, 31 of 36 disks were displaced. In total, 28 of 31 displaced disks showed thickening of the bilaminar zone. In JIA patients, the disks were mainly flattened (19/36), centrally perforated (12/36) and/or anteriorly displaced (2/36). In total, 19 of 31 TMJs with ADD showed various degrees of inflammation, with joint effusion, synovial thickening and joint enhancement not significantly different from JIA patients. Osseous deformity was present in 27 of 31 TMJs with ADD, with frequent erosions in both groups (ADD 25/31; JIA 32/36, P = 0.55) but lower grades of condylar and temporal bone flattening than in JIA (P ≤ 0.001). Glenoid fossa depth was preserved in 28 of 31 joints with ADD and decreased in 26 of 36 joints with JIA (P < 0.0001). Mandibular ramus height was decreased in both groups. CONCLUSION: In adolescents, inflammatory signs are common MRI findings in symptomatic TMJs with ADD and thus should not be considered diagnostic for JIA involvement. In this cohort, both entities had high rates of condylar deformity, while TMJs with ADD showed a better-preserved and often normal shape of the glenoid fossa.

The Swiss French version of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR).

The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the Swiss French language. The reading comprehension of the questionnaire was tested in ten JIA parents and patients. Each participating centre was asked to collect demographic, clinical data, and the JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their parents. The statistical validation phase explored descriptive statistics and the psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling effects, internal consistency, Cronbach's alpha, interscale correlations, test-retest reliability, and construct validity (convergent and discriminant validity). A total of 98 JIA patients (3.1% systemic, 43.9% oligoarticular, 16.3% RF negative polyarthritis, 36.7% other categories), and 64 healthy children were enrolled in a paediatric rheumatology centre. The JAMAR components discriminated well healthy subjects from JIA patients. All JAMAR components revealed good psychometric performances. In conclusion, the Swiss French version of the JAMAR is a valid tool for the assessment of children with JIA and is suitable for use both in routine clinical practice and clinical research.

Identification of an Amino Acid Motif in HLA-DRß1 That Distinguishes Uveitis in Patients With Juvenile Idiopathic Arthritis.

OBJECTIVE: Uveitis is a visually debilitating disorder that affects up to 30% of children with the most common forms of juvenile idiopathic arthritis (JIA). The disease mechanisms predisposing only a subgroup of children to uveitis are unknown. This study was undertaken to identify genetic susceptibility loci for uveitis in JIA, using a genome-wide association study in 522 children with JIA. METHODS: Two cohorts of JIA patients with ophthalmologic follow-up data were genotyped. Data were then imputed using a genome-wide imputation reference panel, and an HLA-specific reference panel was used for imputing amino acids and HLA types in the major histocompatibility complex (MHC). After imputation, genome-wide and MHC-specific analyses were performed, and a reverse immunology approach was utilized to model antigen presentation at 13 common HLA-DRß1 alleles. RESULTS: Presence of the amino acid serine at position 11 (serine 11) in HLA-DRß1 was associated with an increased risk of uveitis in JIA patients (odds ratio [OR] 2.60, P = 5.43 × 10-10 ) and was specific to girls (Pfemales = 7.61 × 10-10 versus Pmales = 0.18). Serine 11 resides in the YST motif in the peptide-binding groove of HLA-DRß1; all 3 amino acids in this motif are in perfect linkage disequilibrium and show identical association with disease. Quantitative prediction of binding affinity revealed that HLA-DRß1 alleles with the YST motif could be distinguished on the basis of discernable peptide-binding preferences. CONCLUSION: These findings highlight a genetically distinct, sexually dimorphic feature of JIA with uveitis as compared to JIA without uveitis. The association could be indicative of the potential involvement of antigen presentation by HLA-DRß1 in the development of uveitis in JIA. The results of this study may advance our progress toward improved treatments for, and possible prevention of, the sight-threatening complications of uveitis in children with JIA.

Toward Establishing a Standardized Magnetic Resonance Imaging Scoring System for Temporomandibular Joints in Juvenile Idiopathic Arthritis.

OBJECTIVE: The temporomandibular joints (TMJs) are frequently affected in children with juvenile idiopathic arthritis (JIA). Early detection is challenging, as major variation is present in scoring TMJ pathology on magnetic resonance imaging (MRI). Consensus-driven development and validation of an MRI scoring system for TMJs has important clinical utility in timely improvement of diagnosis and serving as an outcome measure. We report on a multi-institutional collaboration toward developing a TMJ MRI scoring system for JIA. METHODS: Seven readers independently assessed MRI scans from 21 patients (42 TMJs, from patients ages 6-16 years) using 3 existing MRI scoring systems from American, German, and Swiss institutions. Reliability scores, scoring system definitions, and items were discussed among 10 JIA experts through 2 rounds of Delphi surveys, nominal group voting, and subsequent consensus meetings to create a novel TMJ MRI scoring system. RESULTS: Average-measure absolute agreement intraclass correlation coefficients (avICCs) for the total scores of all 3 scoring systems were highly reliable at 0.96 each. Osteochondral items showed higher reliability than inflammatory items. An additive system was deemed preferable for assessing minor joint changes over time. Eight items were considered sufficiently reliable and/or important for integration into the consensus scoring system: bone marrow edema and enhancement (avICC 0.57-0.61, smallest detectable difference [SDD] ± 45-63% prior to redefining), condylar flattening (avICC 0.95-0.96, SDD ± 23-28%), effusions (avICC 0.85-0.88, SDD ± 25-26%), erosions (avICC 0.94, SDD ± 20%), synovial enhancement and thickening (previously combined, avICC 0.90-0.91, SDD ± 33%), and disk abnormalities (avICC 0.90, SDD ± 19%). CONCLUSION: A novel TMJ MRI scoring system was developed by consensus. Further iterative refinements and reliability testing are warranted in upcoming studies.

Parameters affecting length of stay in a pediatric emergency department: a retrospective observational study.

Prolonged emergency department (ED) length of stay (LOS) is used as a proxy for ED overcrowding and is associated with adverse outcomes of patients requiring therapy and reduced patient satisfaction. Our aim was to identify and quantify variables which affect ED-LOS. Patients admitted to the pediatric ED of a large regional Swiss hospital during a 1-year period were analyzed for LOS (in minutes). Predictor variables included patient-associated parameters (time of admission and discharge, ED occupancy, triage score, diagnosis, and demographic data) and external factors (weekday, time, and season). A total of 4885 visits were included in a multivariable logistic regression analysis. Median LOS was 124 min. The most important factors associated with prolonged LOS were physician referral (adjusted odds ratio [OR], 1.97; 95% confidence interval [CI], 1.47-2.62); morning admissions, especially before noon (OR, 1.92; 95% CI, 1.23-3.07); and gastrointestinal infections (OR, 1.38; 95% CI, 1.08-1.76). Upper airway infections (OR, 0.37; 95% CI, 0.27-0.49) and triage level 5 (OR, 0.18; 95% CI, 0.06-0.61) were inversely associated with ED-LOS. Together with ED occupancy, these factors did significantly contribute to log LOS in a stepwise backward multiple regression model (p < 0.001). CONCLUSION: Several parameters are associated with prolonged ED-LOS. Notably, morning arrivals represent possible targets for strategies to reduce LOS. What is Known: • Prolonged length of stay (LOS) may affect care delivered to admitted patients in the emergency department (ED) and is well studied in the setting of adult patients with high acuity conditions. • Little is known about parameters which impact LOS in European pediatric EDs. What is New: • Several predictors of prolonged LOS could be identified in a European pediatric setting. • Our results indicate that prolonged LOS is associated with modifiable factors like morning and summer admission, which have the potential to be addressed by modification in staffing, infrastructure, and higher attention to faster processing.

Clinical Orofacial Examination in Juvenile Idiopathic Arthritis: International Consensus-based Recommendations for Monitoring Patients in Clinical Practice and Research Studies.

OBJECTIVE: To develop international consensus-based recommendations for the orofacial examination of patients with juvenile idiopathic arthritis (JIA), for use in clinical practice and research. METHODS: Using a sequential phased approach, a multidisciplinary task force developed and evaluated a set of recommendations for the orofacial examination of patients with JIA. Phase 1: A Delphi survey was conducted among 40 expert physicians and dentists with the aim of identifying and ranking the importance of items for inclusion. Phase 2: The task force developed consensus about the domains and items to be included in the recommendations. Phase 3: A systematic literature review was performed to assess the evidence supporting the consensus-based recommendations. Phase 4: An independent group of orofacial and JIA experts were invited to assess the content validity of the task force's recommendations. RESULTS: Five recommendations were developed to assess the following 5 domains: medical history, orofacial symptoms, muscle and temporomandibular joint function, orofacial function, and dentofacial growth. After application of data search criteria, 56 articles were included in the systematic review. The level of evidence for the 5 recommendations was derived primarily from descriptive studies, such as cross-sectional and case-control studies. CONCLUSION: Five recommendations are proposed for the orofacial examination of patients with JIA to improve the clinical practice and aid standardized data collection for future studies. The task force has formulated a future research program based on the proposed recommendations.

Prevalence of Anti-infliximab Antibodies and Their Associated Co-factors in Children with Refractory Arthritis and/or Uveitis: A Retrospective Longitudinal Cohort Study.

OBJECTIVE: Infliximab (IFX) is a monoclonal tumor necrosis factor-α-inhibiting antibody used in children with refractory arthritis and uveitis. Immunogenicity is associated with a lack of clinical response and infusion reactions in adults; data on immunogenicity in children treated with IFX for rheumatic diseases are scarce. We aimed to describe the prevalence of anti-IFX antibodies and determine co-factors associated with anti-IFX antibodies in children with inflammatory rheumatic and ocular diseases. METHODS: Consecutive children treated between August 2009 and August 2012 with IFX at our department were included. Blood samples were collected every 6 months before IFX infusion and tested for anti-IFX antibodies by radioimmunoassay. Patients' charts were retrospectively reviewed for clinical features and analyzed for associations with anti-IFX antibodies. RESULTS: Anti-IFX antibodies occurred in 14/62 children (23%) and 32/253 blood samples (12.6%) after a mean treatment time of 1084 days (range 73-3498). Infusion reactions occurred in 10/62 (16%) children during the treatment period. With continuation of IFX, anti-IFX antibodies disappeared in 7/14 children. In the bivariate analysis, the occurrence of anti-IFX antibodies was associated with younger age at IFX treatment start (mean age 7.01 vs 9.88 yrs, p = 0.003) and infusion reactions (OR 15.0), while uveitis as treatment indication was protective against development of anti-IFX antibodies (OR 0.17), likely because of higher IFX doses. In the multivariate logistic regression, all 3 covariates remained highly significant. CONCLUSION: Anti-IFX antibodies occurred commonly at any time during IFX treatment. Anti-IFX antibodies were associated with younger age at IFX start, infusion reactions, and arthritis as treatment indication.

Temporomandibular Joint Involvement in Association With Quality of Life, Disability, and High Disease Activity in Juvenile Idiopathic Arthritis.

OBJECTIVE: To evaluate the demographic, disease activity, disability, and health-related quality of life (HRQOL) differences between children with juvenile idiopathic arthritis (JIA) and their healthy peers, and between children with JIA with and without clinical temporomandibular joint (TMJ) involvement and its determinants. METHODS: This study is based on a cross-sectional cohort of 3,343 children with JIA and 3,409 healthy peers, enrolled in the Pediatric Rheumatology International Trials Organisation HRQOL study or in the methotrexate trial. Potential determinants of TMJ involvement included demographic, disease activity, disability, and HRQOL measures selected through univariate and multivariable logistic regression. RESULTS: Clinical TMJ involvement was observed in 387 of 3,343 children with JIA (11.6%). Children with TMJ involvement, compared to those without, more often had polyarticular disease course (95% versus 70%), higher Juvenile Arthritis Disease Activity Score (odds ratio [OR] 4.6), more disability, and lower HRQOL. Children with TMJ involvement experienced clearly more disability and lower HRQOL compared to their healthy peers. The multivariable analysis showed that cervical spine involvement (OR 4.6), disease duration >4.4 years (OR 2.8), and having more disability (Childhood Health Assessment Questionnaire Disability Index >0.625) (OR 1.6) were the most important determinants for TMJ involvement. CONCLUSION: Clinical TMJ involvement in JIA is associated with higher disease activity, higher disability, and impaired HRQOL. Our findings indicate the need for dedicated clinical and imaging evaluation of TMJ arthritis, especially in children with cervical spine involvement, polyarticular course, and longer disease duration.

Is early TMJ involvement in children with juvenile idiopathic arthritis clinically detectable? Clinical examination of the TMJ in comparison with contrast enhanced MRI in patients with juvenile idiopathic arthritis.

BACKGROUND: To test clinical findings associated with early temporomandibular joint (TMJ) arthritis in comparison to the current gold standard contrast enhanced magnetic resonance imaging (MRI) in children with juvenile idiopathic arthritis (JIA). METHODS: Seventy-six consecutive JIA patients were included in this study. Rheumatological and orthodontic examinations were performed blinded to MRI findings. Joint effusion and/or increased contrast enhancement of synovium or bone as well as TMJ deformity were assessed on MRI and compared to clinical findings. The maximal mouth opening capacity (MOC) of the JIA patients was compared to normative values obtained from a cohort of 20719 school children from Zürich, Switzerland. RESULTS: On MRI a total of 54/76 (71%) patients and 92/152 (61%) joints had signs of TMJ involvement. MRI showed enhancement in 85/152 (56%) and deformity in 39/152 (26%) joints. MOC, asymmetry and restriction in condylar translation showed significant correlation to TMJ enhancement and deformity, whereas antegonial notching was correlated with TMJ deformity only. When joints with deformity were excluded, enhancement alone did not show a significant correlation with any clinical factor. CONCLUSIONS: Clinical findings in affected TMJs are correlated with structural damage only. Therefore clinical assessment of TMJs does not allow to diagnose early arthritis accurately and will still depend on contrast enhanced MRI.

Magnetic Resonance Imaging Assessment of Temporomandibular Joint Involvement and Mandibular Growth Following Corticosteroid Injection in Juvenile Idiopathic Arthritis.

OBJECTIVE: To assess whether intraarticular corticosteroid injection (CSI) reduces inflammation of the temporomandibular joint (TMJ), prevents growth disturbances of the mandibular condyle, and restores normal growth of the mandibular ramus. METHODS: Retrospective longitudinal magnetic resonance imaging (MRI) evaluation of inflammatory activity, TMJ deformity, and mandibular ramus height in 33 children (23 girls, median age 5.2 yrs) over a median period of 5 years following repetitive CSI to the TMJ. RESULTS: Intraarticular location of CSI led to inflammatory grade improvement in 53% at first MRI followup compared to 20% with extraarticular location (p = 0.005), with more improvement of the mean inflammatory grade after intraarticular CSI (p = 0.001). Rate of osseous deformities of the TMJ deteriorated from 51% at study inclusion to 62% at end of observation period, with progression to severe condylar destruction in 26% of joints including 24% with development of intraarticular calcifications/ossifications. Mean short-term growth rates of the mandibular ramus were negative for intraarticular CSI while positive for extraarticular CSI (p = 0.036). Mean longterm mandibular ramus growth rate (0.7 ± 0.8 mm/yr) after CSI was significantly lower than reported normal mean age- and sex-matched growth rate (1.4 ± 0.1 mm/yr, p < 0.0001). CONCLUSION: Despite improving the inflammatory activity as seen on MRI, repetitive CSI to the TMJ does not reach the treatment goals to prevent progressive osseous deformation and to normalize mandibular ramus growth in children with juvenile idiopathic arthritis.

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.

Infliximab in pediatric rheumatology patients: a retrospective analysis of infusion reactions and severe adverse events during 2246 infusions over 12 years.

OBJECTIVE: To describe infusion reactions (IR) and severe adverse events (SAE) associated with infliximab (IFX) in pediatric patients with rheumatologic and ocular inflammatory diseases in a real-world setting. METHODS: This is a retrospective chart review of all patients treated with IFX at the pediatric rheumatology division of a university hospital between October 2000 and December 2012. RESULTS: A total of 2446 IFX infusions were given to 82 patients (72% female). IR occurred in 46 infusions (2%) of 14 patients (17%) after a mean IFX treatment time of 340 days (range 41-780); 9/14 patients (64%) experienced repeated IR. IR were classified as mild (26%), moderate (74%), or severe (0%). Indications for IFX were arthritis (60%), uveitis (20%), arthritis and uveitis (13%), and other inflammatory diseases (5%). The most common clinical symptoms were respiratory signs (72%), cutaneous manifestations (69%), and malaise (61%). In 6/14 patients (43%) with IR, IFX was discontinued: 4 patients because of repeated IR and 2 patients wished to stop treatment immediately following a mild IR. The other 8/14 patients (57%) received premedication with high-dose antihistamine (100%), corticosteroids (75%), and IFX dose increase (75%) and continued IFX treatment for a mean followup period of 146 weeks (range 26-537) after the first IR. We observed severe infections in 5/82 patients (6%); other SAE were rare. CONCLUSION: Mild and moderate IR occurred in 17% of our patients. Treatment with antihistamines and methylprednisolone, and increasing the IFX dose, allowed continued treatment despite IR in > 50% of patients. Other SAE were infrequent.