Intraocular inflammation in childhood represents a major clinical challenge as if untreated the disease can lead to severe complications and permanent vision loss. The onset is often paucisymptomatic, resulting in delayed detection and consequently a high risk of amblyopia. Pediatric uveitis is classified into idiopathic and associated forms. In juvenile idiopathic arthritis, it is considered an extra-articular manifestation. Among the most common systemic associations are sarcoidosis, tubulointerstitial nephritis and uveitis (TINU) syndrome, Behçet's disease and Vogt-Koyanagi-Harada syndrome. Less frequent, although always to be excluded, is an infectious etiology. As in adults, anterior uveitis is the predominant form in children, followed by intermediate, posterior and panuveitis. Depending on the predominant site of inflammation, key clinical findings and ancillary testing, a differential diagnostic work-up is required to initiate an individualized treatment strategy.

Background Juvenile psoriatic arthritis and enthesitis-related arthritis are two categories of juvenile idiopathic arthritis (JIA). Despite available treatments including non-steroidal anti-inflammatory drugs, glucocorticoids, conventional synthetic disease-modifying antirheumatic drugs (DMARDs), and biological DMARDs, a substantial proportion of people do not adequately respond to treatment or do not have long-lasting clinical remission. The aim of this trial was to show the efficacy and safety of ixekizumab in children with active enthesitis-related arthritis and juvenile psoriatic arthritis. Methods COSPIRIT-JIA is an ongoing multicentre, open-label, phase 3 study of ixekizumab, with a randomised adalimumab reference group, in children with a diagnosis of enthesitis-related arthritis (aged 6 to <18 years) and juvenile psoriatic arthritis (aged 2 to <18 years). Eligible participants had three or more active peripheral joints (presence of swelling or limited motion with pain or tenderness) and a bodyweight of at least 10 kg. Participants received subcutaneous administration of either ixekizumab or adalimumab using a weight-based dosing regimen (ixekizumab 40-160 mg starting dose then 20-80 mg once every 4 weeks; and adalimumab 20-40 mg once every 2 weeks). The primary endpoint was the percentage of ixekizumab-treated participants meeting the JIA-American College of Rheumatology (ACR) 30 (defined as at least 30% improvement from baseline in three of any six core outcome variables, with no more than one of the other variables worsening by more than 30%) response criteria at week 16. A Bayesian analysis was used to assess JIA-ACR30 response rate at week 16. Safety data were summarised using descriptive statistics for all participants who received at least one dose of either treatment. People with lived experience of JIA were not involved in the design or conduct of this study. The trial was registered with ClinicalTrials.gov, NCT04527380. Findings The study enrolled 101 patients (ixekizumab n=81, adalimumab n=20) between April 13, 2021, and April 2, 2024, of whom the initial 40 participants naive to biological DMARD treatment were randomly assigned 1:1 to ixekizumab or adalimumab and the additional 61 participants were assigned to ixekizumab. Of the 81 participants who received ixekizumab, 60 were biological DMARD naive (40 with enthesitis-related arthritis and 20 with juvenile psoriatic arthritis) and 21 were biological DMARD experienced (14 with enthesitis-related arthritis and seven with juvenile psoriatic arthritis). The median age of the participants in the ixekizumab group was 14 years (12 & centerdot;0-15 & centerdot;0), ofwhom 36 (44%) of 81 were female, and 69 (85%) of 81 were White. At week 16, 90% (54 of 60; 95% CI 82 center dot 4-97 center dot 6) of biological DMARD-naive participants and 86% (18 of 21; 70 center dot 7-100 center dot 0) of biological DMARDexperienced participants receiving ixekizumab had a JIA-ACR30 response. Treatment-emergent adverse events were mostly mild (46%) or moderate (36%) for the ixekizumab group, with no severe treatment-emergent adverse events reported. The safety profile was consistent with adult psoriatic arthritis or spondyloarthritis and paediatric psoriasis indications. Interpretation Ixekizumab was well tolerated and effective for the treatment of children with enthesitis-related arthritis and juvenile psoriatic arthritis who are candidates for biological DMARD therapy.

INTRODUCTION:Assessment of disease activity in juvenile systemic sclerosis (jSSc) is essential for clinical care and trial readiness, yet no validated pediatric activity measures exist. Adult systemic sclerosis activity tools, including the Scleroderma Clinical Trials Consortium Activity Index, revised CRISS, and revised EUSTAR, provide conceptual frameworks but require adaptation for developmental, physiologic, and feasibility considerations for children. At the 17th Hamburg Symposium on JSSc, an international multidisciplinary panel reviewed adult indices, evaluated corresponding variables in the jSSc Inception Cohort and the NRCOS registry, and conducted a structured Delphi process to define organ-specific indicators of clinically meaningful activity in jSSc. AREAS COVERED:Across skin, pulmonary, cardiac, vascular, musculoskeletal, gastrointestinal, renal, and global domains, the panel reached broad and often unanimous consensus on variables reflecting active, potentially reversible disease. Key endorsed measures included mRSS progression, new ILD on HRCT, ≥10% declines in FVC or DLCO, new cardiac abnormalities, active digital ulcers, synovitis, myositis, nutritional decline, and physician global assessment. Patient-reported outcomes were strongly supported across domains. EXPERT OPINION:These consensus-derived indicators provide the first comprehensive pediatric-specific foundation for defining disease activity in jSSc and represent a critical step toward developing and validating a unified pediatric activity index suitable for future clinical trials.

Chronic anterior uveitis represents the most important extra-articular manifestation of Juvenile Idiopathic Arthritis (JIA). Previous reviews have shown that outcome measures for this condition are widely heterogeneous. Therefore, our aim was to update the 2019 systematic literature review and to identify similarities, differences, and emerging outcome domains reported over the subsequent five years. We performed a systematic literature review from 1st January 2019 to 28th February 2025 to identify studies investigating outcome measures used in JIA-associated uveitis (JIA-U), according to PRISMA guidelines. We identified 261 papers, of whom 90 potentially eligible. After the full-text revision, 37 studies plus the previous 27, including 1 randomized clinical trial (RCT), were included. Among these studies, 15 outcome measures for JIA-U were identified. Based on their characteristics, we categorized them into three different subgroups: outcome measures for disease activity (30 studies); outcome measures correlated to structural damage (29 studies); and outcome measures of severe disease course (20 studies). The most frequent outcome measures used were the assessment of anterior chamber (AC) cells (29 studies), the visual acuity (21 studies), the development of structural complications (20 studies) and the use and sparing of immunosuppressive therapies (15 studies). Compared with the 2019 review, we identified four studies reporting novel objective techniques for inflammation assessment, including laser flare photometry and anterior segment optical coherence tomography. Our review confirms the variety of outcome measures for JIA-U while highlighting the emergence of novel imaging and biomarker-based measures. These findings provide an updated evidence base for revising the core outcome set and emphasize the urgent need for a consensus and a composite score, which are essential both for designing endpoints in clinical trials and for guiding treatment choices in clinical practice.

BACKGROUND:Juvenile psoriatic arthritis and enthesitis-related arthritis are two categories of juvenile idiopathic arthritis (JIA). Despite available treatments including non-steroidal anti-inflammatory drugs, glucocorticoids, conventional synthetic disease-modifying antirheumatic drugs (DMARDs), and biological DMARDs, a substantial proportion of people do not adequately respond to treatment or do not have long-lasting clinical remission. The aim of this trial was to show the efficacy and safety of ixekizumab in children with active enthesitis-related arthritis and juvenile psoriatic arthritis. METHODS:COSPIRIT-JIA is an ongoing multicentre, open-label, phase 3 study of ixekizumab, with a randomised adalimumab reference group, in children with a diagnosis of enthesitis-related arthritis (aged 6 to <18 years) and juvenile psoriatic arthritis (aged 2 to <18 years). Eligible participants had three or more active peripheral joints (presence of swelling or limited motion with pain or tenderness) and a bodyweight of at least 10 kg. Participants received subcutaneous administration of either ixekizumab or adalimumab using a weight-based dosing regimen (ixekizumab 40-160 mg starting dose then 20-80 mg once every 4 weeks; and adalimumab 20-40 mg once every 2 weeks). The primary endpoint was the percentage of ixekizumab-treated participants meeting the JIA-American College of Rheumatology (ACR) 30 (defined as at least 30% improvement from baseline in three of any six core outcome variables, with no more than one of the other variables worsening by more than 30%) response criteria at week 16. A Bayesian analysis was used to assess JIA-ACR30 response rate at week 16. Safety data were summarised using descriptive statistics for all participants who received at least one dose of either treatment. People with lived experience of JIA were not involved in the design or conduct of this study. The trial was registered with ClinicalTrials.gov, NCT04527380. FINDINGS:The study enrolled 101 patients (ixekizumab n=81, adalimumab n=20) between April 13, 2021, and April 2, 2024, of whom the initial 40 participants naive to biological DMARD treatment were randomly assigned 1:1 to ixekizumab or adalimumab and the additional 61 participants were assigned to ixekizumab. Of the 81 participants who received ixekizumab, 60 were biological DMARD naive (40 with enthesitis-related arthritis and 20 with juvenile psoriatic arthritis) and 21 were biological DMARD experienced (14 with enthesitis-related arthritis and seven with juvenile psoriatic arthritis). The median age of the participants in the ixekizumab group was 14 years (12·0-15·0), of whom 36 (44%) of 81 were female, and 69 (85%) of 81 were White. At week 16, 90% (54 of 60; 95% CI 82·4-97·6) of biological DMARD-naive participants and 86% (18 of 21; 70·7-100·0) of biological DMARD-experienced participants receiving ixekizumab had a JIA-ACR30 response. Treatment-emergent adverse events were mostly mild (46%) or moderate (36%) for the ixekizumab group, with no severe treatment-emergent adverse events reported. The safety profile was consistent with adult psoriatic arthritis or spondyloarthritis and paediatric psoriasis indications. INTERPRETATION:Ixekizumab was well tolerated and effective for the treatment of children with enthesitis-related arthritis and juvenile psoriatic arthritis who are candidates for biological DMARD therapy. FUNDING:Eli Lilly and Company.

INTRODUCTION:Juvenile idiopathic arthritis associated anterior uveitis (JIA-U) is the most common extraarticular manifestation of JIA. There are no published proposed criteria or outcome measures for a 12-month clinical trial for JIA-U. AREAS COVERED:Our expert group, the Multinational Interdisciplinary Working Group for Uveitis in Childhood (MIWGUC), reviewed the previous trials, the quality-of-life instruments, biomarkers, and the patient perspective. Based on an expert consensus, a proposal for a future clinical trial was developed, to provide a foundation for the standardization of outcome measures and trial design in JIA-U. By integrating clinical, imaging, biomarker, and patient-reported outcomes into a unified framework, we aim to accelerate evidence-based therapeutic development and improve long-term care for children affected by anterior uveitis. EXPERT OPINION:A key measure of primary outcome is the anterior chamber cell number, which has intra-observer and inter-observer variation. New techniques that are objective and decrease the variation of the assessment are emerging. Anterior Segmentation Optical Coherence Tomography (OCT) is an innovative imaging technology to assess the number of anterior chamber cells in OCT. The flare meter is an additional assessment, although not yet widely used.

To identify serum biomarkers associated with the development of uveitis in a German juvenile idiopathic arthritis (JIA) cohort. A convenience sample, enriched for uveitis cases, was drawn from a prospectively followed inception cohort of newly diagnosed JIA patients (ICON). Baseline serum samples were biobanked, and each was tested for conventional and novel autoantibodies using multi-analyte array technologies. Associations between uveitis occurrence, disease outcomes, and autoantibody profiles were examined. Fifty-two patients with and 141 patients without uveitis were included in the analyses. At first uveitis documentation, 26

Objectives To determine the prevalence of depressive and anxiety symptoms among young people 7 years and 9 years after inclusion in the multicentre, prospective inception cohort (ICON) of newly diagnosed patients with juvenile idiopathic arthritis (JIA) in Germany, and to identify factors associated with mental health problems at study inclusion and in the course of the disease.Methods Patients and controls (healthy peers, eg, friends of the same age and sex) from the ICON cohort (both ≥13 years) were assessed for mental health using the Patient Health Questionnaire-9 and the Generalised Anxiety Disorder Scale-7 at 7-year and 9-year follow-ups. Demographic and clinical characteristics, treatments and health-related quality of life (HRQoL) (Pediatric Quality of Life Inventory (PedsQL)) were documented at baseline and follow-up visits. Cross-sectional (analysis of variance or χ² tests at 7-year/9-year follow-up) and longitudinal analyses (generalised linear mixed models for PedsQL in follow-up from baseline) were conducted, respectively.Results A total of 344 patients (age 18.7±3.5 years, disease duration 9.2±1.8 years, 42% polyarthritis) and 224 controls (age 18.2±3.6 years) were evaluated. Moderate to severe symptoms of depression and anxiety were present in 13% and 10% of patients, respectively, compared with 7% and 2% of controls. Patients with moderate to severe psychological distress did not exhibit significantly higher physician-reported disease activity at inclusion and follow-up but reported worse patient-reported outcomes. These patients already showed reduced emotional functioning 3 months after diagnosis (p<0.001) and reported lower physical and emotional functioning (p<0.001) after the first year of specialised care compared with those without relevant mental health problems at long-term follow-up.Conclusion Poor emotional functioning at the start of care for JIA may be an indicator of future mental health issues. Therefore, HRQoL should be routinely assessed at treatment initiation to identify at-risk patients early and provide targeted support.

Objectives:Clinical trial data are lacking for treatment of patients with juvenile systemic sclerosis (jSSc). Three published recommendations exist for jSSc but real-world data on treatment patterns are lacking. The aim of this study was to analyse treatments used in the jSSc inception cohort (jSSci) and compare to published recommendations on the treatment of jSSc. Methods:Data was extracted for patients with 24 months follow-up visits in the jSSci up until June 2023. Medications used and their association with clinical characteristics were analysed. Logistic regression analyses were performed to compare treatments between limited and diffuse cutaneous jSSc subtypes, organ involvement and time of initiation of treatment. Multilevel mixed effects logistic regression analyses were used to evaluate the change in medication use in follow-up. Treatment patterns were compared against published recommendations. Results:93 patients had 24 months follow-up data. 77% of patients were receiving disease-modifying treatment (DMARD) at enrolment, which increased to 91% at 24 months (p<0.001). Patients with diffuse cutaneous jSSc subtype had significantly more frequently active ulcerations, skin involvement and received any kind of treatment more often compared with limited (97% vs 91%, p=0.047). Methotrexate was used in 52% of patients at enrolment which decreased to 37% at 24 months (p=0.001). Mycophenolate mofetil use increased from 24% to 46% (p<0.001). Biological DMARDs increased from 5% to 22% (p<0.001). The treatment pattern strongly overlapped with the published paediatric guidance. Conclusion:This is the first report regarding the pattern of medication use in real life in the currently largest patient cohort of patients with jSSc. The observed pattern overlaps with the published recommendations.

Die intraokulare Entzündung im Kindesalter stellt eine bedeutende Herausforderung dar, da sie unbehandelt zu schweren Komplikationen mit Sehverlust führen kann. Sie beginnt oft symptomarm, wird verzögert erkannt und birgt damit ein hohes Amblyopierisiko. Die Erkrankung wird in idiopathische und assoziierte Formen differenziert. Bei der juvenilen idiopathischen Arthritis wird sie als extraartikuläre Manifestation betrachtet. Zu den häufigsten systemischen Erkrankungen zählen Sarkoidose, TINU-, Behçet- und das Vogt-Koyanagi-Harada-Syndrom. Seltener – aber stets auszuschließen – ist eine infektiöse Genese. Auch im Kindesalter dominiert die anteriore Entzündungsform gefolgt von intermediärer, posteriorer und Panuveitis. Abhängig vom Schwerpunkt der Entzündung, von Leitbefunden und Zusatzuntersuchungen sollte eine differenzialdiagnostische Einordnung erfolgen, um eine individuell angepasste Therapie einzuleiten.

Juvenile systemic sclerosis (jSSc) is a rare multisystem autoimmune disease, representing 4-10 % of systemic sclerosis (SSc) cases, and causes significant morbidity during growth and development. While sharing features with adult-onset disease, jSSc differs in phenotype, with more frequent diffuse cutaneous involvement, overlap syndromes, distinct autoantibody profiles and different outcomes. Evidence to guide care remains limited because of disease rarity and the lack of paediatric trials. This review summarises epidemiology, classification, clinical features and outcomes of jSSc, highlighting differences from adult disease. A structured approach to assessment is presented, emphasizing regular multisystem evaluation. Organ-specific assessment of skin, lung, cardiac, gastrointestinal, musculoskeletal, renal and vascular involvement, alongside patient- and parent-reported outcomes, is discussed. Management strategies are reviewed using paediatric consensus recommendations and extrapolated adult data, emphasizing specialist paediatric rheumatology care within multidisciplinary teams. Emerging therapies, including autologous haematopoietic stem cell transplantation, and issues of psychosocial impact and transition to adult care are addressed.