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Purpose: To determine whether a 12-week, lower body-targeted aqua-plyometric (AquaPlyo) exercise program could improve muscle strength, bone mineral properties, and physical fitness in patients with juvenile idiopathic arthritis. Methods: A randomized controlled trial was adopted and included 48 patients with polyarticular juvenile idiopathic arthritis (age: 12–18 y). Patients were assigned to undergo either AquaPlyo exercises (AquaPlyo group, n = 24) or standard exercises (control group, n = 24). The outcome measures were assessed pretreatment and posttreatment and included concentric quadriceps peak torque, bone mineral properties (areal bone mineral density [BMD], volumetric BMD, bone mineral content, and BMD Z score), and physical fitness. Results: A significant posttreatment increase in the concentric quadriceps peak torque was detected in the AquaPlyo group compared with the control group (either at an angular velocity of 90°/s [right side: P =.016, left side: P =.025] or 180°/s [right side: P =.007, left side: P =.029]). Besides, a considerably greater improvement in the areal BMD (P =.0006), volumetric BMD (P =.027), bone mineral content (P =.002), and BMD Z score (P =.0004) was observed in the AquaPlyo group. Moreover, a remarkably greater rise in the physical fitness (P <.001) was revealed in the AquaPlyo group. Conclusion: AquaPlyo training can efficiently enhance muscle strength, improve bone mineral properties, and boost physical fitness in patients with juvenile idiopathic arthritis. [ABSTRACT FROM AUTHOR]

Purpose: Evaluate the response to adalimumab (ADA) in pediatric chronic anterior uveitis (pCAU). Methods: Retrospective chart review of pCAU patients treated with ADA. Outcomes evaluated included the proportion of patients achieving zero ocular inflammation and discontinuation of topical corticosteroids, visual outcomes, and incidence of uveitis recurrences after ≥ 12 months of prescribing ADA. Incidence and risk factors for developing anti-adalimumab antibodies (AAAs) were also evaluated. Results: Of 27 children aged 11 years, 16 (59%) were Caucasian and 6 (22%) African Americans. Thirteen (48%) patients had idiopathic pCAU, 12 (44%) had juvenile idiopathic arthritis (JIA) related pCAU, and 2 (7%) had tubulointerstitial nephritis and uveitis syndrome. At baseline, African American children had worse visual acuity (p = 0.026). At 1 year, 21 (78%) children achieved zero ocular inflammation (remission). Risk factors associated with non-remission were being African American (20% vs. 94%, p = 0.003) and experiencing ≥ 1 episode of uveitis recurrence (100% vs. 0%, p < 0.001). Six episodes of uveitis recurrence were documented in five children, four of whom were African American. Topical corticosteroids were discontinued in 83% of children, and visual acuity remained stable for 1 year. Twelve children were tested for AAAs due to arthritis or uveitis flare-ups, with five (42%) being positive. No significant factors were associated with the development of AAAs. Conclusions: We found that ADA is effective in controlling inflammation, reducing the need for topical corticosteroids, and maintaining visual acuity in pCAU. There appears to be racial differences in African American children who had worse baseline disease and poorer outcomes. Studies are necessary to understand better and address these disparities. [ABSTRACT FROM AUTHOR]

Background The genetic architecture of JIA remains only partially comprehended. There is a clear imperative for continued endeavours to uncover insights into the underlying causes of JIA. Methods This study encompassed a comprehensive spectrum of endeavours, including conducting a JIA genome-wide association study (GWAS) meta-analysis that incorporated data from 4550 JIA cases and 18 446 controls. We employed in silico and genome-editing approaches to prioritizing target genes. To investigate pleiotropic effects, we conducted phenome-wide association studies. Cell-type enrichment analyses were performed by integrating bulk and single-cell sequencing data. Finally, we delved into potential druggable targets for JIA. Results Fourteen genome-wide significant non-HLA loci were identified, including four novel loci, each exhibiting pleiotropic associations with other autoimmune diseases or musculoskeletal traits. We uncovered strong genetic correlation between JIA and BMD traits at 52 genomic regions, including three GWAS loci for JIA. Candidate genes with immune functions were captured by in silico analyses at each novel locus, with additional findings identified through our experimental approach. Cell-type enrichment analysis revealed 21 specific immune cell types crucial for the affected organs in JIA, indicating their potential contribution to the disease. Finally, 24 known or candidate druggable target genes were prioritized. Conclusions Our identification of four novel JIA-associated genes, CD247 , RHOH , COLEC10 and IRF8 , broadens the novel potential drug repositioning opportunities. We established a new genetic link between COLEC10 , TNFRSF11B and JIA/BMD. Additionally, the identification of RHOH underscores its role in positive thymocyte selection, thereby illuminating a critical facet of JIA's underlying biological mechanisms. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to report the interim 5-year safety and effectiveness of abatacept in patients with JIA in the PRINTO/PRCSG registry. Methods The Abatacept JIA Registry (NCT01357668) is an ongoing observational study of children with JIA receiving abatacept; enrolment started in January 2013. Clinical sites enrolled patients with JIA starting or currently receiving abatacept. Eligible patients were assessed for safety (primary end point) and effectiveness over 10 years. Effectiveness was measured by clinical 10-joint Juvenile Arthritis Disease Activity Score (cJADAS10) in patients with JIA over 5 years. As-observed analysis is presented according to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. Results As of 31 March 2020, 587 patients were enrolled; 569 are included in this analysis (including 134 new users) with 1214.6 patient-years of safety data available. Over 5 years, the incidence rate (IR) per 100 patient-years of follow-up of serious adverse events was 5.52 (95% CI: 4.27, 7.01) and of events of special interest was 3.62 (95% CI: 2.63, 4.86), with 18 serious infections [IR 1.48 (95% CI: 0.88, 2.34)]. As early as month 3, 55.9% of patients achieved cJADAS10 low disease activity and inactive disease (20.3%, 72/354 and 35.6%, 126/354, respectively), sustained over 5 years. Disease activity measures improvement over 5 years across JIA categories. Conclusion Abatacept was well tolerated in patients with JIA, with no new safety signals identified and with well-controlled disease activity, including some patients achieving inactive disease or remission. Trial registration Clinicaltrials.gov, NCT01357668. [ABSTRACT FROM AUTHOR]

Objective To quantify differences in hospital-associated costs, and accompanying travel costs and productivity losses, before and after withdrawing TNF-α inhibitors (TNFi) in JIA patients. Methods This was a retrospective analysis of prospectively collected data from electronic medical records of paediatric JIA patients treated with TNFi, which were immediately discontinued, spaced (increased treatment interval) or tapered (reduced subsequent doses). Costs of hospital-associated resource use (consultations, medication, radiology procedures, laboratory testing, procedures under general anaesthesia, hospitalization) and associated travel costs and productivity losses were quantified during clinically inactive disease until TNFi withdrawal (pre-withdrawal period) and compared with costs during the first and second year after withdrawal initiation (first and second year post-withdrawal). Results Fifty-six patients were included of whom 26 immediately discontinued TNFi, 30 spaced and zero tapered. Mean annual costs were €9165/patient on active treatment (pre-withdrawal) and decreased significantly to €5063/patient (−44.8%) and €6569/patient (−28.3%) in the first and second year post-withdrawal, respectively (P  < 0.05). Of these total annual costs, travel costs plus productivity losses were €834/patient, €1180/patient, and €1320/patient in the three periods respectively. Medication comprised 80.7%, 61.5% and 72.4% of total annual costs in the pre-withdrawal, first and second year post-withdrawal period, respectively. Conclusion In the first two years after initiating withdrawal, the total annual costs were decreased compared with the pre-withdrawal period. However, cost reductions were lower in the second year compared with the first year post-withdrawal, primarily due to restarting or intensifying biologics. To support biologic withdrawal decisions, future research should assess the full long-term societal cost impacts, and include all biologics. [ABSTRACT FROM AUTHOR]

Objective Diagnostic pitfalls often arise in the community because of potentially misleading similarities between juvenile idiopathic arthritis (JIA) and Blau syndrome, an immune-related disorder caused by NOD2 gene mutations. It remains unclear in which population and to what extent next-generation sequencing techniques can aid in diagnosis. Methods We evaluated clinical usefulness of targeted next-generation sequencing in previously diagnosed JIA. Participants were required to have symptoms and signs suspected of Blau syndrome, including at least uveitis or cutaneous lesions in addition to arthritis. Targeted sequencing was conducted on NOD2 gene to detect diagnostic variants classified as pathogenic or likely pathogenic for Blau syndrome. We assessed the molecular diagnostic yield and clinical implications for patient care. Results Between 1 May 2008 and 1 June 2021, sequencing data were accrued from 123 previously diagnosed JIA (median age: 5 years; female: 62.6%). Targeted NOD2 sequencing yielded a positive molecular diagnosis of Blau syndrome in 21.1% (95% CI: 14.9%, 29.2%), encompassing six heterozygous missense mutations classified as pathogenic variants. Among those receiving a molecular diagnosis, changes in clinical management and treatment were considered as having occurred in 38.5%. Nine predictors were identified as being associated with a higher diagnostic yield, providing clinical clues to suspect the possibility of Blau syndrome. Conclusion Among some patients with paediatric-onset arthritis complicated with uveitis or cutaneous lesions, reassessment of the diagnosis of JIA may be warranted. Targeted NOD2 sequencing established the molecular diagnosis of Blau syndrome in nearly one-fifth of these cases and provided clinically relevant information for patient-care decisions. [ABSTRACT FROM AUTHOR]

Objectives To describe the clinical features and treatment outcomes of children with juvenile psoriatic arthritis (JPsA) and compare the distinct patterns of the disease between early-onset and late-onset age groups. Methods Patients with JPsA followed regularly for at least 6 months between 2010 and 2020 in seven paediatric rheumatology centres in Turkey were included in the study. The demographic features, clinical manifestations, treatment strategies and outcomes of the patients were evaluated retrospectively. Results A total of 87 (46 male/41 female) patients were included in the study. The mean age at diagnosis was 11.9 years (s. d. 4.5). Fifty-seven (65.5%) patients had psoriasis at the time of diagnosis and arthritis preceded psoriasis in 10 (11.5%) patients. Thirty (34.5%) patients had dactylitis, 28 (32.2%) had nail pitting, 36 (41.4%) had involvement of the small joints and 20 (23%) had enthesitis. Sacroiliitis was detected in 11 (12.6%) patients by MRI. ANA was positive in 35 (40.2%) patients. Twelve children (13.8%) were in the early-onset (<5 years) group. Uveitis and ANA positivity were more common in the early-onset group. Active joint counts and activity scores of our patients showed significant improvement at month 6 and at the last control compared with baseline. Conclusion About one-third of patients with JPsA do not have psoriasis at the time of diagnosis. In some patients, no skin lesion is seen during the course of the disease. Children with PsA seem to display two different phenotypes. Younger children have a female predominance, ANA positivity and uveitis, while older children have more axial involvement. [ABSTRACT FROM AUTHOR]

Background: Fever of unknown origin (FUO) is a common condition worldwide in children that remains a diagnostic challenge. The causes of FUO vary depending on the patient's age, residency, and the time of study. Therefore, this study aimed to identify the common aetiologies of FUO at Alexandria University Children's Hospital under the current diagnostic abilities and newly emerging diseases. Methods: The current prospective observational study included all children fulfilling the definition of FUO admitted at Alexandria University Children's Hospital from January 2020 to December 2021 using a steps approach for investigations. Results: A total of 110 children with fever of unknown origin (FUO) were included in this study; the average duration of fever was 36.76 ± 31.73 days. In most of the enrolled cases 105/110 (95.4%) the definite etiology of FUO was identified. The common causes were collagen vascular diseases (30.9%), infectious diseases (28.2%), miscellaneous conditions (19.1%), and malignancy (17.3%). Among collagen vascular diseases, systemic lupus erythematosus (SLE) (47.1%) and systemic onset juvenile idiopathic arthritis (sJIA) (38.2%) were the most common. In the infectious category, Katayama fever (16.1%), brucellosis (12.9%), and urinary tract infection (UTI) (12.9%) were the most frequently observed. Post-Covid MIS-C (52.4%) was the most common in the miscellaneous category. Children in the infectious category had significantly higher neutrophil [5.76 (2.28–7.92) × 10^3/µl] and lymphocytic counts [ 4.2 (2.04–5.91) × 10^3/µl]; (P < 0.001 and < 0.010 respectively). Moreover, in the collagen category the median lymphocytic count was lower [1.95 (1.47–2.73) × 10^3/µl] with a significantly (P < 0.010) higher neutrophil/ lymphocyte ratio [2.30 (1.53–3.91)]. Conclusion: Collagen vascular diseases, infectious diseases, miscellaneous, and malignancy were the most common causes of FUO. Katayama fever, urinary tract infections (UTI), and brucellosis were the most common causes in the infectious category. Post-Covid MIS-C and hemophagocytic lymphohistiocytosis were the most common diagnoses in the miscellaneous category. [ABSTRACT FROM AUTHOR]

Background: Juvenile idiopathic arthritis (JIA) is the most common chronic inflammatory rheumatic disease in children, and adalimumab is one of the primary treatment options. Although it is widely used for inflammatory diseases, there is limited research on its safety and efficacy in patients with psychiatric disorders or in those with inflammatory diseases who also have comorbid psychiatric conditions. Case report: We report a 12-year-old adolescent boy who presented with emotional instability for 1 year, exacerbated leading to hospital admission in the past month. Upon detailed evaluation after admission, it was found that the patient's emotional fluctuations may be related to the use of Adalimumab. Follow-up after psychiatric inpatient treatment revealed that the patient did not experience emotional excitement again after discontinuing Adalimumab. Conclusions: Although tumor necrosis factor-α inhibitors have positive effects on the emotional, cognitive, and physical functions of patients with inflammatory diseases, their use may induce mood swings in patients with comorbid mood disorders. This is particularly important for adolescents with rapid mood changes, where greater caution is required. Further research is necessary to clarify the correlation between the adverse effects of these drugs and their impact on patients with bipolar disorder. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic has significantly impacted individuals with chronic conditions. This investigation assessed the quality of care provided to pediatric and adolescent patients with juvenile idiopathic arthritis (JIA) during the pandemic in Thailand. Methods: This cross-sectional analysis enrolled JIA patients aged ≤ 18 years at an academic tertiary care facility from April 2022 to March 2023. Retrospective reviews were performed, complemented by patient and caregiver questionnaires to assess the pandemic's impact on care quality. Results: Seventy JIA patients (37 males, 33 females) with a mean age of 13.5 ± 3.1 years were included. A total of 41.4% of the caregivers reported negative impacts on JIA care due to the pandemic and the lockdown, and 31.4% of the patients experienced pandemic-related anxiety. A comparison between the pandemic and prepandemic periods revealed a higher incidence of active disease, although the difference was statistically nonsignificant (37.1% vs 14.2%, p = 0.106). Nonadherence significantly predicted active disease status (adjusted OR 15.04, 95% CI 2.48–91.15, p = 0.03). COVID-19 vaccinations were administered to 85.7% of patients; 52.8% of whom contracted mild COVID-19. Most patients (71.4%) postponed clinic visits; 36% due to lockdowns and 28% due to concerns about COVID-19 exposure in healthcare settings. The majority of patients received telephone JIA management advice from rheumatologists during the lockdown (91.4%). Conclusions: The COVID-19 pandemic and associated lockdown measures affected the care of JIA patients, impacting both physical and mental health. Nonadherence was a critical factor in disease flare-ups. Telemedicine is indispensable for patient care. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to evaluate through analysis using CBCT the transverse and axial diameters of the mandibular condyles in subjects affected by juvenile idiopathic arthritis (JIA) and compare them with those of healthy subjects. Methods: The study was conducted on CBCT scans from the digital archive of the Department of Biomedical Surgical and Dental Sciences, University of Milan, including patients with JIA and using healthy subjects as controls. Inclusion criteria: aged between 7 and 25 years old at the time of the CBCT examination; Caucasian ethnicity; diagnosis of JIA according to the International League of Associations for Rheumatology (ILAR) criteria documented in patients' records; TMJ involvement; good quality CBCTs covering our region of interest (ROI), from the glabella to the mandibular inferior border; no previous orthodontic/orthopedic treatment; no history of craniofacial trauma or congenital birth defects involving the craniofacial area. Each CBCT scan underwent examination using 3Diagnosys® software. Since data were normally distributed, parametric tests were used for analysis. The sample was divided into three groups: (1) bilateral JIA subjects, (2) unilateral JIA subjects, and (3) healthy controls. Results: We found a statistically significant reduction (p < 0.0001) in the transverse diameter (TR-Diam) of the affected condyles by an average of 1.7 mm, while the axial diameter (AX-Diam) again showed a slight reduction, on average by 0.1 mm, with a non-statistically significant value. Another comparison was made between the unaffected condyles of patients with unilateral JIA and the healthy condyles of the control group. The unilateral unaffected condyles were found to be slightly smaller than those of healthy patients, but without statistically significant differences. We found that in both JIA males and females, the condylar growth tends to stop earlier than the healthy ones. Conclusions: The transverse diameter was found to be more affected than the axial one, causing typical bone resorption and condylar shape. Moreover, we showed that the pathology, in the case of unilateral JIA, does not compromise only the affected condyles; the corresponding condyle that seems to be healthy is actually partially compromised. In addition, we observed that the growth of affected condyles of JIA subjects tends to stop earlier than the condyles of the healthy controls. [ABSTRACT FROM AUTHOR]

Objective Previous epidemiological data of JIA in Finland are from the turn of the millennium. We aimed to determine the recent annual incidence of JIA in several consecutive years in Finland and to explore the differences in incidence between sexes, age groups and regions. Methods We analysed all children <16 years of age who met the ILAR classification criteria for JIA. Cases from 2000–2020 were identified from two national registers: the Care Register for Health Care of the Finnish Institute for Health and Welfare and the Reimbursement Register containing medication data from the Social Insurance Institution of Finland; cases from 2016–2020 were identified from the Finnish Rheumatology Quality Register. Results The incidence of JIA was 31.7 per 100 000 (95% CI 30.2, 33.1), according to the Care Register in 2000–2020 and peaked in 2010–2014. No considerable differences in incidence rates were observed among registers. In all age groups, incidence in girls was predominant compared with boys. The incidence in girls peaked at the ages of 2 years and 14–15 years. Decreasing incidence was observed among boys 0–3 years old during the entire study period, whereas increasing incidence was observed among teenage girls and boys 4–7 years old in 2000–2013. Conclusion The incidence of JIA is not only very high with respect to that in other parts of the world but also higher than previously reported in Finland. The incidence varied by region and year but was not higher at the end than the beginning of the study period. [ABSTRACT FROM AUTHOR]

Objective To investigate the safety and efficacy of subcutaneous tocilizumab (SC-TCZ) treatment in a long-term extension (LTE) of clinical trials in polyarticular or systemic juvenile idiopathic arthritis (pJIA or sJIA). Methods Patients with pJIA or sJIA from two open-label, 52-week phase 1b core trials of SC-TCZ who had adequate response per investigator assessment entered the LTE and continued SC-TCZ treatment according to body weight–based dosing regimens until commercial availability or up to 5 years. Pharmacokinetics, pharmacodynamics, and efficacy were assessed for up to 3 years, and safety for up to 5 years in the LTE. Results Forty-four patients with pJIA and 38 patients with sJIA entered the LTE. Tocilizumab trough concentrations were maintained within the range expected to provide clinical benefit (mean values: pJIA, ∼10 μg/ml; sJIA, ∼75 μg/ml over 3 years). Pharmacodynamic parameters (interleukin-6, soluble interleukin-6 receptor, erythrocyte sedimentation rate, C-reactive protein) were maintained throughout the LTE at levels achieved in the core trials. Inactive disease per American College of Rheumatology provisional criteria was reported for 90% (17/19) and 53% (8/15) of patients with pJIA and 91% (10/11) and 92% (12/13) of patients with sJIA in the <30 and ≥30 kg body weight groups, respectively. Serious adverse events in the LTE were reported in six patients with pJIA (13.6%; five serious infections) and five patients with sJIA (13.2%; one serious infection). Conclusion Patients with pJIA or sJIA experienced long-term disease control with SC-TCZ treatment. Long-term safety was consistent with the known tocilizumab safety profile. Clinical trial registration clinicaltrials.gov, NCT02165345 [ABSTRACT FROM AUTHOR]

Objectives: Our study aimed to evaluate the relationship of small joint involvement with demographic, clinical, and laboratory findings and to determine its possible effects on prognosis. Methods: This retrospective observational study was conducted in patients diagnosed with oligoarticular juvenile idiopathic arthritis (oJIA) in the paediatric rheumatology department of Ankara City Hospital between April 2009 and September 2022. The relationship between small joint involvement and demographic, clinical, and laboratory findings and prognosis was investigated by statistical methods with the data recorded from the medical records of oJIA patients. Results: Of the 198 patients diagnosed with oJIA, small joint involvement was observed in a total of 20 (10%) patients, 11 (5.5%) at the time of diagnosis, and 9 (4.5%) during the follow-up period. The frequency of small joint involvement in extended oJIA was significantly higher than in persistent oJIA (P = .001). Patients with small joint involvement had significantly higher erythrocyte sedimentation rate and C-reactive protein values at admission (P = .047, P = .038) and Juvenile Arthritis Disease Activity Score at 3, 6, and 12 months (P = .001, P = .001, P = .018). The need for conventional disease-modifying antirheumatic drugs and biologic disease-modifying antirheumatic drugs was significantly higher in patients with small joint involvement (P = .001, P = .001). Conclusions: oJIA patients with small joint involvement may have higher acute phase reactants at diagnosis, a more extended course and active disease in follow-up, and the need for treatment escalation. [ABSTRACT FROM AUTHOR]

Objective: We assessed and compared molecular tissue changes at the entheses in patients with psoriasis (PsO) and psoriatic arthritis (PsA) and in healthy controls (HCs) in vivo using multispectral optoacoustic tomography (MSOT) and described their relationship with clinical and ultrasound findings of enthesitis. Methods: A cross‐sectional study (MSOT and Arthrosonography in PsA) in biologic disease‐modifying antirheumatic drug–naïve patients with PsA and PsO and HCs was performed. Participants underwent clinical, ultrasonographic, and MSOT examination of six entheses (lateral humeral epicondyle, distal patellar tendon attachment, and Achilles tendon attachment). MSOT‐measured hemoglobin (Hb), oxygen saturation (SO2), collagen, and lipid levels were quantified, and mean differences between groups were calculated using linear mixed effects models. MSOT‐measured analytes were compared between entheses with and without clinical and ultrasound anomalies. Results: Ninety participants were included (30 PsO, 30 PsA, and 30 HCs), 540 entheses were clinically assessed, and 540 ultrasound and 830 MSOT scans were obtained. Patients with PsA and PsO showed increased oxygenated Hb (PsA: P = 0.003; PsO: P = 0.054) and SO2 (PsA: P < 0.001; PsO: P = 0.001) levels and decreased collagen signals (PsA: P < 0.001; PsO: P < 0.001) compared with HCs, with more pronounced changes in PsA. Significantly lower collagen levels (P = 0.01) and increased lipids (P = 0.03) were recorded in tender entheses compared with nontender ones. Erosions and enthesophytes on ultrasound were associated with significant differences in SO2 (P = 0.014) and lipid signals (P = 0.020), respectively. Conclusion: Patients with PsA and PsO exhibit an analogous metabolic pattern at the entheses that is exacerbated in the presence of inflammation. These findings support the notion of a psoriatic disease spectrum characterized by common immunometabolic tissue changes. [ABSTRACT FROM AUTHOR]

Objective: The objective is to characterize transcriptomic profiles and immune cell composition and distribution in juvenile idiopathic arthritis (JIA) synovial biopsies, assess for associations of these features with clinical parameters, and compare JIA and rheumatoid arthritis (RA) synovial features. Methods: RNA sequencing (RNASeq) was performed on 24 samples, with pathway analysis and inference of relative abundance of immune cell subsets based on gene expression data. Two multiplex fluorescence immunohistochemistry (IHC) panels were performed on 28 samples (including 13 on which RNASeq was performed), staining for CD206− classical and CD206+ nonclassical macrophages, and CD8+ and CD4+ T and B lymphocytes. Data were compared to a published series of early RA synovial biopsies. Results: Pathway analysis of the most variably expressed genes (n = 339) identified a B and plasma cell signature as the main driver of heterogeneity in JIA synovia, with strong overlap between JIA and RA synovitis. Multiplex IHC confirmed heterogeneity of immune cell infiltration. M1‐like macrophage–rich synovial lining was associated with greater lining hypertrophy and higher (CD45+) pan–immune cell and CD8+ T cell infiltration. Conclusion: Our study indicates significant similarities between JIA and RA synovitis. Similar to RA, JIA synovia may be broadly categorized into two groups: (1) those with an inflammatory/adaptive immune transcriptomic signature, M1‐like macrophage and CD8+ T cell infiltration, and thicker, M1‐like macrophage–rich synovial lining, and (2) those with an M2‐like macrophage transcriptomic signature, greater M2/M1‐like macrophage ratios, and thinner, M2‐like macrophage–rich synovial lining. Synovial features were not significantly associated with clinical parameters, likely because of group size and heterogeneity. [ABSTRACT FROM AUTHOR]

Objective: Our objective was to develop and validate cutoff values in the systemic Juvenile Arthritis Disease Activity Score 10 (sJADAS10) that distinguish the states of inactive disease (ID), minimal disease activity (MDA), moderate disease activity (MoDA), and high disease activity (HDA) in children with systemic juvenile idiopathic arthritis, based on subjective disease state assessment by the treating pediatric rheumatologist. Methods: The cutoff definition cohort was composed of 400 patients enrolled at 30 pediatric rheumatology centers in 11 countries. Using the subjective physician rating as an external criterion, six methods were applied to identify the cutoffs: mapping, calculation of percentiles of cumulative score distribution, the Youden index, 90% specificity, maximum agreement, and receiver operating characteristic curve analysis. Sixty percent of the patients were assigned to the definition cohort, and 40% were assigned to the validation cohort. Cutoff validation was conducted by assessing discriminative ability. Results: The sJADAS10 cutoffs that separated ID from MDA, MDA from MoDA, and MoDA from HDA were ≤2.9, ≤10, and >20.6, respectively. The cutoffs discriminated strongly among different levels of pain, between patients with and without morning stiffness, and among patients whose parents judged their disease status as remission or persistent activity or flare or were satisfied or not satisfied with current illness outcome. Conclusion: The sJADAS cutoffs revealed good metrologic properties in both definition and validation cohorts and are therefore suitable for use in clinical trials and routine practice. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to present the demographic, clinical, laboratory, and treatment data of children with non-infectious uveitis and to evaluate the risk factors for the development of complications and the need for biological treatment. Method: Patients diagnosed with non-infectious uveitis in childhood and followed up for at least 1 year were included in the study. Demographic data, including age, gender, age at diagnosis, uveitis in first-degree relatives, and rheumatologic diseases, were obtained retrospectively from medical records. The presence of complications or the need for biologic therapy was considered a composite outcome suggesting severe disease. Results: The study included 123 patients (female: n = 59, 48%). The mean age at diagnosis was 14.89 ± 4.86 years. Uveitis was symptomatic in 104 patients (84.6%). Approximately one-quarter of the patients had at least one rheumatic disease (n = 35, 28.5%), the most common being juvenile idiopathic arthritis. Thirty-three patients (26.8%) had anti-nuclear antibody positivity. Biologic agents were needed in 60 patients (48.8%). Complications developed in 14 patients (11.4%). Early age at disease onset (aOR, 0.875; 95% C.I. 0.795–0.965, p = 0.007) and female gender (aOR, 2.99; 95% C.I. 1.439–6.248, p = 0.003) were significantly associated with the need for biologic treatment, while Behçet's disease (BD) was strongly associated with uveitis-related complications (aOR, 14.133; 95% C.I. 2.765–72.231, p = 0.001). Conclusion: We suggest that among pediatric patients with non-infectious uveitis, females, those with an early age of disease onset, and those with BD need to be closely monitored due to a significantly increased risk of severe disease. Key Points • Limited data exist on the clinical course of non-infectious uveitis in children and the associated risk factors for severe disease. • Our study reveals that nearly a quarter of pediatric patients with non-infectious uveitis also have a rheumatic disease. • Among pediatric patients diagnosed with non-infectious uveitis, we observed an increased risk of severe disease in those with an earlier onset age, in female patients, and in those diagnosed with Behçet's disease. [ABSTRACT FROM AUTHOR]

Objective: Diagnosing juvenile idiopathic arthritis (JIA) is challenging. Our study aimed to investigate the clinical significance of anti-α-1,4-D-polygalacturonic acid (PGA) antibodies in JIA, focusing on their role in diagnosis and assessing disease activity. Methods: In this prospective case–control study, we examined variations in serum levels of PGA-IgA and PGA-IgG among children with different types of JIA and healthy controls. Serum PGA-IgA and PGA-IgG levels were assessed concurrently in children with active and inactive JIA. Results: This study included 126 patients diagnosed with JIA, 13 neonates, and 76 healthy children. Serum PGA-IgA and PGA-IgG levels were assessed, which revealed significant differences in PGA-IgA levels between various JIA subtypes and controls. An analysis of PGA-IgA levels in various JIA states revealed a statistically significant difference. Receiver operating characteristic (ROC) analysis demonstrated the robust predictive capability of PGA-IgA, with an AUC of 0.879 (p < 0.001), along with a specificity of 0.842 and sensitivity of 0.848. Conclusion: Increased levels of anti-PGA antibodies, particularly PGA-IgA, were significantly associated with JIA. PGA-IgA may serve as a sensitive biomarker for disease activity in JIA and could potentially aid in the diagnosis of JIA. Key Points • This study found a significant correlation between blood levels of PGA-IgA and juvenile idiopathic arthritis (JIA), which may provide valuable diagnostic insights. • PGA-IgA shows potential as a sensitive biomarker for the assessment of disease activity in JIA patients, helping to determine disease activity. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the use of two self‐management intervention strategies for persistent fatigue in adolescents and young adults with a fatigue syndrome or rheumatic condition. Design: A randomized crossover trial administering tailored lifestyle advice and generic dietary advice, each 12 weeks, with a four‐week washout period between. Methods: Sixty participants (aged 12–29) were included. Tailoring was achieved through the PROfeel method. Dietary guidelines were conceptualized by the Netherlands Nutrition Centre. Questionnaires were used pre–post‐interventions to measure primary outcome 'fatigue severity' (Checklist Individual Strength‐8) and secondary outcomes 'self‐efficacy' (Self‐Efficacy Scale‐28) and 'quality of life' (QoL) (Paediatric Quality of Life Inventory 4.0). Feasibility and adherence were self‐rated on a scale of 1 to 10 (low to high). Linear mixed modelling was used to assess change over time, compare strategy effectiveness and study the impact of intervention order. Results: Fatigue severity, self‐efficacy and QoL regarding 'physical' and 'emotional' functioning improved significantly over time (all p <.015). The average improvement of the two QoL subscales was clinically relevant, as was the fatigue improvement in 20 out of 46 participants who completed the trial and 5 dropouts. The interventions were equally effective, and intervention order did not impact the improvement level (prange =.242–.984). The self‐management strategies received similar feasibility (M = 6.45, SD = 1.91) and adherence (M = 7.67, SD = 1.67) ratings. Conclusions: As small to clinically relevant improvements were observed, self‐management strategies might be particularly useful to bridge waiting time for guided treatments such as Cognitive Behavioural Therapy. [ABSTRACT FROM AUTHOR]

Juvenile idiopathic arthritis is the most common rheumatic disorder in childhood and adolescence posing a significant threat of short-term and long-term disability if left untreated. Methotrexate is a folic acid analog with various immunomodulatory properties. It has demonstrated significant efficacy for the treatment of juvenile idiopathic arthritis, often considered the preferred first-line disease-modifying anti-rheumatic drug given as monotherapy or in combination with biological drugs. Despite this, there is a considerable risk for treatment disruptions owing to the high prevalence of methotrexate intolerance, with symptoms such as nausea, stomach ache, vomiting, and behavioral symptoms. Many different risk factors for the intolerance have been proposed including gender, age, disease activity, treatment duration, dosing and administration, and genetic and psychological factors. As the studies have shown contradictory results, many questions are left unanswered. Therefore, a consensus regarding outcome measures and reporting is crucial. In this review, we describe the identification and assessment of methotrexate intolerance and evaluate potential risk factors, genetic associations as well as management strategies. [ABSTRACT FROM AUTHOR]

Aim: Higher adiposity and increased risk of cardiovascular diseases have been reported in juvenile idiopathic arthritis (JIA), but body composition measurements have produced inconsistent results. This controlled cross‐sectional study assessed body composition with two methods to evaluate adiposity in children with JIA. Methods: We measured body composition by dual‐ energy X‐ray absorptiometry (DXA) and bioelectrical impedance analysis (BIA) from 79 JIA‐patients in two Finish university hospitals in 2017–2019. Their age‐ and sex‐matched controls (n = 79) were selected from the Physical Activity and Nutrition in Children‐ study and through National Registry. Results: Body fat percentage measured by BIA was higher (mean, SD) in patients compared to controls (23.1 ± 9.3% vs. 20.1 ± 7.5%, p = 0.047). Also, using DXA, there was a tendency of higher body fat percentage in patients (27.1 ± 9.1% vs. 24.6 ± 8.6, p = 0.106). BIA and DXA showed strong correlation (r from 0.810 to 0.977) in all body composition variables. Conclusion: Increased adiposity was observed in patients with JIA. Evaluation of body composition should be included in the multidisciplinary care of JIA to reduce the possible risk of cardiovascular diseases in adulthood. BIA could be a useful tool for assessing body composition due to its clinical availability and safety. [ABSTRACT FROM AUTHOR]

Systemic juvenile idiopathic arthritis (sJIA) is a severe inflammatory condition with onset in childhood. It is sporadic, but elements of its stereotypical innate immune responses are likely genetically encoded by both common variants with small effect sizes and rare variants with larger effects. Genomic investigations have defined the unique genetic architecture of sJIA. Identification of the class II HLA locus as the strongest sJIA risk factor for the first time brought attention to T lymphocytes and adaptive immune mechanisms in sJIA. The importance of the human leukocyte antigen (HLA) locus was reinforced by recognition that HLA-DRB1*15 alleles are strongly associated with development of drug reactions and sJIA-associated lung disease (sJIA-LD). At the IL1RN locus, genetic variation relates to both risk of sJIA and may also predict non-response to anakinra. Finally, rare genetic variants may have critical roles in disease complications, such as homozygous LACC1 mutations in families with an sJIA-like illness, and hemophagocytic lymphohistiocytosis (HLH) gene variants in some children with macrophage activation syndrome (MAS). Genetic and genomic analysis of sJIA holds great promise for both basic discovery of the course and complications of sJIA, and may help guide personalized medicine and therapeutic decision-making. [ABSTRACT FROM AUTHOR]

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children. The International League of Associations for Rheumatology (ILAR) has defined JIA as "arthritis of unknown etiology persisting for ≥6 wk with an onset at <16 y of age, after excluding other causes of joint inflammation". Synovial inflammation is the result of a complex interplay of aberrant immune systems (both adaptive and innate) in a genetically susceptible individual, with possible external stimuli/triggers. Diagnosis of JIA essentially remains clinical, and laboratory investigations usually help to assess the severity of disease activity. Few investigations like antinuclear antibodies (ANA), human leukocyte antigen (HLA)-B27, and rheumatoid factor (RF) help to categorize or prognosticate a child with JIA. Timely use of effective therapeutic interventions including biological has shown good long-term outcomes of JIA. [ABSTRACT FROM AUTHOR]

PurposeMethodsResultsConclusionTo demonstrate the efficacy and safety of intravenous golimumab infusion in treating juvenile idiopathic arthritis-associated anterior uveitis.This study was a retrospective observation case series. Electronic records of patients diagnosed with juvenile idiopathic arthritis-associated anterior uveitis who received intravenous golimumab infusion were examined.A total of 24 eyes of 13 patients were included in this study. During 12 months before starting intravenous golimumab, the median grade of anterior chamber reaction was 1 (range: 0.5–3), and the median number of flare-ups was 1 (1–3). During 12 months following the start of intravenous golimumab, the median grade of anterior chamber reaction was 0 (range: 0–1), and the median number of flare-ups was 0 (range: 0–1). Before starting intravenous golimumab, the average number of immunomodulatory agents was 2.6 ± 1.0 with a range of 2 to 5. The average age of patients at the time of starting intravenous golimumab was 13.69 ± 5.23 years (range between 5 and 22). A total of 11 (84.6%) patients responded to intravenous golimumab. The medication was discontinued in one patient due to ineffectiveness and in another patient due to the development of psoriasis as an adverse effect. Cystoid macular edema was present in six eyes of three patients which resolved in all six eyes after starting intravenous golimumab.Intravenous golimumab proves to be efficacious and safe for inducing and sustaining remission in JIA and JIA-associated uveitis. Nonetheless, further robust studies with larger sample sizes are needed to substantiate our findings. [ABSTRACT FROM AUTHOR]