Disease Activity In Juvenile Idiopathic Arthritis Research Articles

Factors determining resistance to conventional disease-modifying anti-rheumatic drug treatment in oligoarticular juvenile idiopathic arthritis.

Our study was designed to investigate the reasons for starting the conventional disease-modifying anti-rheumatic drugs (DMARDs) and the variables that impact the response to DMARD treatment in oligoarticular juvenile idiopathic arthritis (JIA) patients. Oligoarticular JIA patients (n = 187) were categorized into two groups: Group A consisted of patients who achieved remission with DMARD, and Group B comprised those who did not respond to DMARD therapy. DMARDs were initiated for various reasons: 68 (36.4%) due to active disease despite nonsteroidal anti-inflammatory drugs (± intra-articular corticosteroid) treatment, 59 (31.6%) due to uveitis, 49 (26.2%) due to extended oligoarticular JIA, and 11 (5.9%) due to inflammatory bowel disease. One hundred twenty-three patients (65.8%) achieved remission with DMARDs (Group A), while 64 patients (34.2%) did not respond to DMARD therapy (Group B). In Group B, patients had higher C-reactive protein (CRP) levels as well as higher Juvenile Idiopathic Arthritis Disease Activity Scores-71 (JADAS-71) at diagnosis (both p < 0.001). Moreover, extended oligoarticular JIA subtype (p = 0.017) and involvement of small joints at diagnosis (p = 0.043) were more prevalent among these patients. Group A exhibited a higher frequency of antinuclear antibody positivity (p = 0.014). Elevated CRP levels (> 1.1mg/dL) (OR 1.308, 95% CI 1.203-3.574; p < 0.001) and high JADAS-71 at diagnosis (> 15.8) (OR 1.659, 95% CI 1.179-2.941; p < 0.001) were associated with DMARD resistance. Elevated CRP and high JADAS-71 at diagnosis were the main factors associated with DMARD resistance in oligoarticular JIA. Prospective long-term studies may help verify the role of these factors associated with DMARD resistance in oligoarticular JIA. Key Points • Conventional DMARDs were most commonly started due to active disease despite NSAID (± intra-articular corticosteroids). • Remission was achieved with DMARD in 65.8% of oligoarticular JIA patients. • Elevated CRP and high JADAS-71 at diagnosis were associated with DMARD resistance.

Validation of new medication use algorithms as proxies for worsening disease activity in patients with juvenile idiopathic arthritis.

To facilitate claims-based research on populations with juvenile idiopathic arthritis (JIA), we sought to validate an algorithm of new medication use as a proxy for worsening JIA disease activity. Using electronic health record data from three pediatric centers, we defined new JIA medication use as (re)initiation of disease-modifying antirheumatic drugs or glucocorticoids (oral or intra-articular). Data were collected from 201 randomly selected subjects with (101) or without (100) new medication use. We assessed the positive predictive value (PPV) and negative predictive value (NPV) based on a reference standard of documented worsening of JIA disease activity. The algorithm was refined to optimize test characteristics. Overall, the medication-based algorithm had suboptimal performance in representing worsening JIA disease activity (PPV 69.3%, NPV 77.1%). However, algorithm performance improved for definitions specifying longer times after JIA diagnosis (≥1-year post-diagnosis: PPV 82.9%, NPV 80.0%) or after initiation of prior JIA treatment (≥1-year post-treatment: PPV 89.7%, NPV 80.0%). An algorithm for new JIA medication use appears to be a reasonable proxy for worsening JIA disease activity, particularly when specifying new use ≥1 year since initiating a prior JIA medication. This algorithm will be valuable for conducting research on JIA populations within administrative claims databases.

Examining the Relationship between Systemic Immune-Inflammation Index and Disease Severity in Juvenile Idiopathic Arthritis.

Juvenile Idiopathic Arthritis (JIA), the leading childhood rheumatic condition, has a chronic course in which persistent disease activity leads to long-term consequences. In the era of biologic therapy and tailored treatment, precise disease activity assessment and aggressive intervention for high disease activity are crucial for improved outcomes. As inflammation is a fundamental aspect of JIA, evaluating it reflects disease severity. Recently, there has been growing interest in investigating cellular immune inflammation indices such as the neutrophil-to-lymphocyte ratio (NLR) and systemic immune inflammation index (SII) as measures of disease severity. The aim of this retrospective study was to explore the potential of the SII in reflecting both inflammation and disease severity in children with JIA. The study comprised 74 JIA patients and 50 healthy controls. The results reveal a notable increase in median SII values corresponding to disease severity, exhibiting strong correlations with traditional inflammatory markers, including CRP and ESR (ρ = 0.714, ρ = 0.661), as well as the JADAS10 score (ρ = 0.690). Multiple regression analysis revealed the SII to be independently associated with JADAS10. Furthermore, the SII accurately distinguished patients with high disease activity from other severity groups (AUC = 0.827, sensitivity 81.5%, specificity 66%). These findings suggest that integrating the SII as an additional measure holds potential for assessing disease activity in JIA.

A decade of progress in juvenile idiopathic athritis treatments and outcomes in Canada: results from ReACCh-Out and the CAPRI registry.

To assess changes in juvenile idiopathic arthritis (JIA) treatments and outcomes in Canada, comparing a 2005-2010 and a 2017-2021 inception cohorts. Patients enrolled within three months of diagnosis in the Research in Arthritis in Canadian Children Emphasizing Outcomes (ReACCh-Out) and the Canadian Alliance of Pediatric Rheumatology Investigators Registry (CAPRI) cohorts were included. Cumulative incidences of drug starts and outcome attainment within 70 weeks of diagnosis were compared with Kaplan Meier survival analysis and multivariable Cox regression. The 2005-2010 and 2017-2021 cohorts included 1128 and 721 patients, respectively. JIA category distribution and baseline clinical juvenile idiopathic arthritis disease activity (cJADAS10) scores at enrolment were comparable. By 70 weeks, 6% of patients (95% CI 5, 7) in the 2005-2010 and 26% (23, 30) in the 2017-2021 cohort had started a biologic DMARD (bDMARD), and 43% (40, 47) and 60% (56, 64) had started a conventional DMARD (cDMARD), respectively. Outcome attainment was 64% (61, 67) and 83% (80, 86) for Inactive disease (Wallace criteria), 69% (66, 72) and 84% (81, 87) for minimally active disease (cJADAS10 criteria), 57% (54, 61) and 63% (59, 68) for pain control (<1/10), and 52% (47, 56) and 54% (48, 60) for a good health-related quality of life. Although baseline disease characteristics were comparable in the 2005-2010 and 2017-2021 cohorts, cDMARD and bDMARD use increased with a concurrent increase in minimally active and inactive disease. Improvements in parent and patient reported outcomes were smaller than improvements in disease activity.

Knee acoustic emissions as a noninvasive biomarker of articular health in patients with juvenile idiopathic arthritis: a clinical validation in an extended study population

BackgroundJoint acoustic emissions from knees have been evaluated as a convenient, non-invasive digital biomarker of inflammatory knee involvement in a small cohort of children with Juvenile Idiopathic Arthritis (JIA). The objective of the present study was to validate this in a larger cohort.FindingsA total of 116 subjects (86 JIA and 30 healthy controls) participated in this study. Of the 86 subjects with JIA, 43 subjects had active knee involvement at the time of study. Joint acoustic emissions were bilaterally recorded, and corresponding signal features were used to train a machine learning algorithm (XGBoost) to classify JIA and healthy knees. All active JIA knees and 80% of the controls were used as training data set, while the remaining knees were used as testing data set. Leave-one-leg-out cross-validation was used for validation on the training data set. Validation on the training and testing set of the classifier resulted in an accuracy of 81.1% and 87.7% respectively. Sensitivity / specificity for the training and testing validation was 88.6% / 72.3% and 88.1% / 83.3%, respectively. The area under the curve of the receiver operating characteristic curve was 0.81 for the developed classifier. The distributions of the joint scores of the active and inactive knees were significantly different.ConclusionJoint acoustic emissions can serve as an inexpensive and easy-to-use digital biomarker to distinguish JIA from healthy controls. Utilizing serial joint acoustic emission recordings can potentially help monitor disease activity in JIA affected joints to enable timely changes in therapy.

Extracellular vesicles in systemic juvenile idiopathic arthritis.

Systemic juvenile idiopathic arthritis is a chronic pediatric inflammatory disease of unknown etiology, characterized by fever, rash, hepatosplenomegaly, serositis, and arthritis. We hypothesized that intercellular communication, mediated by extracellular vesicles, contributes to systemic juvenile idiopathic arthritis pathogenesis and that the number and cellular sources of extracellular vesicles would differ between inactive and active states of systemic juvenile idiopathic arthritis and healthy controls. We evaluated plasma from healthy pediatric controls and patients with systemic juvenile idiopathic arthritis with active systemic flare or inactive disease. We isolated extracellular vesicles by size exclusion chromatography and determined total extracellular vesicle abundance and size distribution using microfluidic resistive pulse sensing. Cell-specific extracellular vesicle subpopulations were measured by nanoscale flow cytometry. Isolated extracellular vesicles were validated using a variety of ways, including nanotracking and cryo-electron microscopy. Extracellular vesicle protein content was analyzed in pooled samples using mass spectrometry. Total extracellular vesicle concentration did not significantly differ between controls and patients with systemic juvenile idiopathic arthritis. Extracellular vesicles with diameters <200 nm were the most abundant, including the majority of cell-specific extracellular vesicle subpopulations. Patients with systemic juvenile idiopathic arthritis had significantly higher levels of extracellular vesicles from activated platelets, intermediate monocytes, and chronically activated endothelial cells, with the latter significantly more elevated in active systemic juvenile idiopathic arthritis relative to inactive disease and controls. Protein analysis of isolated extracellular vesicles from active patients showed a proinflammatory profile, uniquely expressing heat shock protein 47, a stress-inducible protein. Our findings indicate that multiple cell types contribute to altered extracellular vesicle profiles in systemic juvenile idiopathic arthritis. The extracellular vesicle differences between systemic juvenile idiopathic arthritis disease states and healthy controls implicate extracellular vesicle-mediated cellular crosstalk as a potential driver of systemic juvenile idiopathic arthritis disease activity.

Paediatric rheumatologists do not score the physician's global assessment of juvenile idiopathic arthritis disease activity in the same way.

To assess the heterogeneity in factors affecting physician's global assessment of disease activity (PhGA) and in PhGA scoring of multiple JIA patient's case scenarios. An electronic web-based questionnaire of factors potentially considered in PhGA was sent worldwide to members of PRINTO and the Pediatric Rheumatology Care and Outcomes Improvement Network (PR-COIN). The respondents were asked to rate from 0 to 100 the relevance of 17 factors possibly affecting PhGA scoring and to derive a PhGA score of 17 detailed JIA patient cases. The median and interquartile range was used to measure the heterogeneity in the scoring. To demonstrate the consistency among the PhGA scores of the patient cases provided by multiple physicians, we assessed the inter-rater reliability using intra-class correlation. The questionnaire was completed by 491 respondents. A large individual variation was observed in the impact of different factors on PhGA when assessing JIA. For non-systemic JIA the presence of fever had the largest variation and swollen joint count had the smallest. For sJIA, the largest variation was seen in the presence of erosions and the smallest in the presence of fever. The intra-class correlation of the group for PhGA scoring of patient cases was 0.53 (95% CI 0.38, 0.72). In a sample of worldwide respondents, the scoring of the PhGA is divergent. Consensus on PhGA scoring guidelines is required to obtain a consistent assessment of patients.

Serum calprotectin and joint ultrasound in the definition of disease relapse in non-systemic juvenile idiopathic arthritis: a prospective longitudinal study.

The aim of our study was to investigate the role of serum calprotectin (SC) and muscle-skeletal ultrasound (MSUS) as predictive markers of relapse in patients with juvenile idiopathic arthritis (JIA). Sixty non-systemic (ns) JIA patients in clinical remission were recruited to evaluate the risk of disease relapse. SC levels and JIA disease activity were assessed at every visit (3, 6, 12 and 18 months). Joint synovitis, characterised by both synovial effusion (SE) and synovial hyperplasia (SH), was measured by US score (sum of SE, SH, power Doppler and bone erosions) given to each examined joint and US ratio (US score/number of joints examined) at every visit. Associations of SC, US score and US ratio with relapse prevalence was studied longitudinally by using generalised estimating equations model. Thirty-one (51.6%) patients relapsed within 18 months. Patients with higher baseline US scores showed higher risk of relapse at 6 months (OR (95% confidence interval (CI)): 1.96 (1.09-3.52)). Additionally, patients with higher SC values at baseline showed higher risk of relapse at 18 months (1.66 (1.13-2.44)). Patients with higher baseline SC values showed an increased overall odds of relapse up to 18 months of follow-up (1.21 (1.08-1.36)). Furthermore, patients with higher US scores showed an increased overall odds of relapse up to 18 months of follow-up (1.96 (1.56-2.46)). Similarly, patients with higher US ratio showed an increased overall odds of relapse up to 18 months of follow-up (16.62 (7.17-38.54)). SC was able to identify JIA patients with unstable remission and increased risk of relapse. MSUS represents an interesting additional tool to the clinical evaluation, especially in predicting early relapse.

Role of CD4+NKG2D+ T cells in the disease activity of juvenile idiopathic arthritis

To study the expression levels of CD4+NKG2D+ T cells and NKG2D soluble ligands, the soluble MHC class I chain-related molecules A and B (sMICA/sMICB) in the active stage and stable stage of juvenile idiopathic arthritis (JIA) and their role in the disease activity of JIA. Nineteen children with systemic JIA and 20 children with articular JIA who were diagnosed in Children's Hospital of Chongqing Medical University from November 2019 to December 2021 were enrolled in this prospective study. Six healthy children were enrolled as the control group. After peripheral blood samples were collected, ELISA was used to measure the levels of sMICA and sMICB, and flow cytometry was used to measure the percentage of CD4+NKG2D+ T cells. Systemic Juvenile Arthritis Disease Activity Score-27 (sJADAS-27)/Juvenile Arthritis Disease Activity Score-27 (JADAS-27) was used to evaluate the disease activity in children with JIA. The Pearson correlation analysis and the receiver operating characteristic (ROC) curve were used to assess the role of CD4+NKG2D+ T cells, sMICA and sMICB in the disease activity of JIA. The active systemic JIA and active articular JIA groups had a significant increase in the percentage of CD4+NKG2D+ T cells compared with the control group and their corresponding inactive JIA group (P<0.05). The JIA groups had significantly higher levels of sMICA and sMICB than the control group (P<0.05), and the active articular JIA group had a significantly higher level of sMICB than the stable articular JIA group (P<0.05). In the children with JIA, the percentage of CD4+NKG2D+ T cells and the levels of sMICA and sMICB were positively correlated with sJADAS-27/JADAS-27 disease activity scores (P<0.05). The ROC curve analysis showed that sMICB had an area under the curve of 0.755 in evaluating the disease activity of JIA, with a specificity of 0.90 and a sensitivity of 0.64. The percentage of CD4+NKG2D+ T cells and the levels of sMICA and sMICB increase in children with JIA compared with healthy children and are positively correlated with the disease activity of JIA, suggesting that CD4+NKG2D+ T cells and NKG2D ligands can be used as potential biomarkers for evaluating the disease activity of JIA.

Haptoglobin in Juvenile Idiopathic Arthritis

BackgroundHaptoglobin (Hp), a liver derived acute phase inflammatory protein (APP), has scarcely been studied in juvenile idiopathic arthritis (JIA). Hp can occur in blood as two isoforms (Hp1 and Hp2) in precursor and mature forms. Routine clinical chemistry immunoturbidimetry does not discern these forms. It is unknown how different forms relate to disease activity in JIA. Our aims were to determine allele frequency and plasma concentrations of different Hp forms at higher versus lower JIA disease activity and compare to other APPs.MethodsPlasma from JIA (n = 77) and healthy (n = 42) children were analyzed for apparent Hp allelic frequency and densitometric concentrations of alpha forms by Western blot (WB). Polymerase chain reaction (PCR) (buffy coat) was performed in a subset to estimate conformity with genetics. At higher versus lower juvenile arthritis disease activity score (JADAS27) (which includes erythrocyte sedimentation rate (ESR)), total mature Hp concentration from WB was compared and correlated against immunoturbidimetry and total protein, albumin, serum amyloid A (SAA) and C-reactive protein (CRP).ResultsAt 300-fold dilution needed to study mature forms in Western blot, precursors were undetectable. Hp2 contributed most signal in most samples. Hp allele frequency was similar in JIA and controls. Both mature forms, taken separately or by sum, declined following treatment, but remained above concentrations of healthy controls, even in a remission subset that achieved JADAS27 < 1. Densitometry correlated with immunoturbidimetry. Hp concentrations correlated with JADAS27, albumin (negatively), CRP and SAA with immunoturbidimetric method correlating strongest to JADAS27 (Spearman R ~ 0.6, p < 0.0001).ConclusionHp allele frequency in JIA is similar to the general population, indicating that children with JIA should have the same possibility as in healthy children to produce preHp2 (zonulin), thought to increase intestinal permeability. Circulating Hp concentrations largely parallel other APPs and ESR; none of these measures correlate very strongly to JADAS27 score but Hp can be measured from capillary sampling which is impossible with ESR.

Obesity as a comorbidity in children and adolescents with autoimmune rheumatic diseases.

Childhood obesity is the public health issue with alarming rates recorded throughout developed world and an important modifiable health risk for developing various chronic diseases, with childhood-onset autoimmune rheumatic diseases among them also. The aim of this article was to summarize epidemiological, pathophysiological and clinical implication of obesity on juvenile idiopathic arthritis (JIA), childhood-onset systemic lupus erythematosus (cSLE), juvenile dermatomyositis (JDM), IgA vasculitis (IgAV) and Kawasaki disease (KD). We reviewed PubMed database and selected 74 relevant articles. Epidemiological data of obesity among children with autoimmune rheumatic diseases indicate an increased prevalence of it. Pathophysiological link between obesity, humoral adipokines and cytokines released from fat tissue and childhood-onset autoimmune rheumatic diseases is complex and still not entirely clear. From the clinical point of view, obesity was not associated with disease activity in JIA and cSLE, but proved to contribute on functional impairment in both diseases and affect poor treatment response in JIA patients. Early atherosclerosis and cardiovascular disease (CVD) development in obese children and adolescents with JIA, cSLE and JDM are certainly important obesity-related complications. Understanding how obesity affects children and adolescents with autoimmune rheumatic diseases may encourage clinicians to consider taking better preventive strategies in this population to improve their long-term outcome.

The role of S100A12 and Toll-like receptor 4 in assessment of disease activity in familial Mediterranean fever and juvenile idiopathic arthritis.

Our aim was to investigate the possible relationship between the serum S100A12 and Toll-like receptor 4 (TLR4) levels, and the activity of familial Mediterranean fever (FMF) and juvenile idiopathic arthritis (JIA) in accordance with the routine biochemical parameters. Furthermore, the effectiveness of these 2 biomarkers in distinguishing FMF from JIA has been evaluated. Sixty-nine children with FMF, 68 children with JIA, and 35 healthy children were included in this study. S100A12 and TLR4 levels were measured by the sandwich enzyme-linked immunosorbent assay technique. In the FMF patient group, serum S100A12 level was found to be significantly higher than in both the JIA and control groups (P=.000 and P=.000, respectively). Although S100A12 levels were higher in the attack period compared to the attack-free period, this increase was not statistically significant (P > .05). TLR4 levels were statistically significantly higher in the attack period compared to the attack-free period in children with FMF (P < .05). Although there was no relationship between S100A12 levels and disease activity, there is a clear correlation between S100A12 and the Auto-Inflammatory Disease Activity Index in attack-free FMF patients (r=0.612 P=.000). Serum S100A12 levels were not found to be a potentially valuable biomarker for assessing disease activity in either FMF or JIA. However, TLR4 levels were found to be a valuable biomarker for assessing disease activity in children with FMF. Further research which includes serial monitoring of S100A12 and TLR4 levels in a large cohort will provide detailed information about accuracy of these 2 potential biomarkers in both patients group.

21 Disease activity and body mass index in juvenile idiopathic arthritis: is the truth revealed?

BackgroundActive disease in chronic rheumatic diseases in adults seems to be associated with overweight and obesity [1]. Juvenile Idiopathic Arthritis (JIA) is the most frequent rheumatic disease in children. The relationship between body mass index (BMI) and disease activity in JIA patients is less studied.ObjectiveTo determine the link between BMI and disease activity in JIA patients.MethodsWe conducted a cross-sectional study including 35 JIA patients meeting the International League of Associations for Rheumatology (ILAR) 2001 criteria.For each patient, we collected the following data: age, age at the onset of JIA, disease duration, patient global assessment (PGA), visual analogic scale (VAS), tender joint count (TJC), swollen joint count (SJC), disease activity using the Juvenile Arthritis Disease Activity score (JADAS), and therapeutic management.The weight and height were measured for each patient. The BMI was calculated and interpreted according to the World Health Organization classification.We also measured C-reactive protein (CRP) and Erythrocyte sedimentation rate (ERS) level.ResultsWe included 15 boys and 20 girls. The mean age was 12.2 ± 3.61 years. The mean age at the onset of the disease was 8.65 ± 3.83 years. The mean disease duration was 4.1 ± 3.29 years.The mean PGA and the mean VAS were 3.4 ± 3.02 and 3.37 ± 2.92, respectively.The mean TJC and the mean SJC were 1.48 ± 1.69 and 0.61 ± 0.77, respectively.The mean CRP and ESR were 7.51 ± 11.85 mg/l and 18.88 ± 15.53 mm, respectively.The mean JADAS was 7.58 ± 6.3. Twenty-four patients were under non-steroidal anti-inflammatory drugs (69%), 10 patients were under methotrexate (34%), and 5 patients were under TNFα inhibitor (14%).The mean BMI was 19.94 ± 5.46 kg/m². Fourteen patients were underweight (40%), 15 patients had a BMI in the normal range (43%), 4 patients were overweight (11%), and 2 patients were obese (6%).Underweight patients had higher PGA, higher CRP level, higher tender joint count (TJC), and higher JADAS compared with overweight and obese patients, but without significant difference (PGA: 2.97 ± 2.6 vs 2 ± 1.89, p = 0.4; CRP: 7.54 ± 15.09 vs 4.25 ± 4.19 mg/l, p = 0.6; TJC: 1.7 ± 1.56 vs 1 ± 0.8, p = 0.3, and JADAS: 6.3 ± 6.18 vs 2.98 ± 2.24, p = 0.1).No correlations were found between BMI and the following parameters: TJC, SJC, EGP, CRP, ESR, and JADAS.ConclusionData about associations between underweight, obesity, and disease activity in JIA are conflicting. Some authors suggested that active disease is associated with adiposity [2]. Others showed that underweight patients had higher disease activity [3]. Although there was no significant difference, our study is consistent with Neto et al. study. Indeed, active disease seems to affect the child’s appetite and weight gain leading to cachexia [3]. Other studies are needed to confirm these results.

Transitioning patients with juvenile idiopathic arthritis to adult care: the Nordic experience

BackgroundWith juvenile idiopathic arthritis (JIA), there are several protocols and practices used worldwide for the transition from paediatric to adult care. In this study, we examined the transferral rates and disease activity after transition, as well as the disease- and health-related outcomes. We also introduce the transition practices employed in the Nordic countries.MethodsThe study population comprised 408 participants with a disease onset from 1997 to 2000 who attended an 18-year follow-up visit in this population-based Nordic JIA cohort study. The patients were retrospectively divided into three subgroups: Patients transferred directly from paediatric care to adult rheumatology care, patients referred there later, and patients never transferred during the 18-year follow-up period.ResultsOne hundred and sixty-three (40%) JIA patients had been directly transferred to an adult clinic. The cumulative transition rate was 52%, but there were significant differences between the participating centres. Fifty patients had later been referred to an adult clinic. Among the 195 patients who had never been transferred, 39% were found to have disease activity at the study visit.ConclusionThis study highlights the need to reconsider transition practices to avoid our undesirable finding of patients with disease activity in JIA, but no appropriate health care follow-up.

Are infections in children with juvenile idiopathic arthritis more frequent than in healthy children? A prospective multicenter observational study.

BackgroundChildren with juvenile idiopathic arthritis (JIA) might be at a higher risk of infection. Our objectives are to describe and compare infection rates in patients with JIA vs. healthy patients.MethodsA prospective, multicenter observational study was performed in Spain from January 2017 to June 2019. Patients with JIA from 7 participating hospitals and children without JIA (siblings of patients with JIA, and non-JIA children from primary health centers) were followed up with quarterly questionnaires to record infection episodes. Tuberculosis, herpes zoster, and infections requiring hospital admission were considered severe infections. Rates of infection (episodes/patient/year) were compared using a generalized estimating equations model.ResultsA total of 371 children (181 with and 190 without JIA) were included. The median age was 8.8 years (IQR 5.5–11.3); 75% of the patients with JIA received immunosuppressive treatment (24% methotrexate, 22% biologic, 26% both). A total of 667 infections were recorded; 15 (2.2%) were considered severe. The infection rate was 1.31 (95%CI 1.1–1.5) in JIA and 1.12 (95%CI 0.9–1.3) in non-JIA participants (p = 0.19). Age <4 years increased the infection rate by 2.5 times (2.72 vs. 1.12, p < 0.001) in both groups. The most frequent infection sites were upper respiratory (62.6% vs. 74.5%) and gastrointestinal (18.8% vs. 11.4%). There were no differences in severe infections (2.5% vs. 2%, p = 0.65) between the groups. In children with JIA, younger age and higher disease activity (JADAS71) were associated with a higher infection rate.ConclusionWe found no differences in the infection rate or infection severity between patients with and without JIA. Most infections were mild. An age younger than 4 years increased the infection risk in both groups. Higher disease activity was associated with a higher infection rate.

Psychological/social factors associated with transfer readiness in young people with juvenile idiopathic arthritis

The aim of this study is to investigate the relationships between psychological/social factors and transfer readiness from paediatric to adult rheumatology services in pre- and post-transfer young people (YP) with juvenile idiopathic arthritis (JIA). Participants completed questionnaires measuring a broad range of psychological/social factors (generalised anxiety, pain-specific anxiety, pain-related thoughts, depression, prosocial behaviours, problem behaviours, arthritis-related quality of life (QoL), social support, family functioning) and transfer readiness (transfer-related knowledge and skills, health-related self-efficacy). JIA disease activity was measured on the same day as the questionnaires. This study received all relevant ethical and regulatory approvals, and informed consent was received from or on behalf of all participants. In total, 40 pre-transfer YP with JIA aged 10-16 years (M = 13.54 years, 26 females) and their parents/guardians participated at Sheffield Children's NHS Foundation Trust, and 40 post-transfer YP with JIA aged 16-24 years (M = 20.16 years, 26 females) participated at Sheffield Teaching Hospitals NHS Foundation Trust. For both pre- and post-transfer YP, greater transfer readiness was associated with lower generalised anxiety levels, lower pain-specific anxiety levels, fewer pain-related thoughts, lower depression levels, fewer problem behaviours, better arthritis-related QoL, better social support, and better family functioning. Greater transfer readiness was also associated with less JIA disease activity for post-transfer YP only. A broad range of psychological/social factors were associated with transfer readiness in pre- and post-transfer YP with JIA. This highlights the importance of assessing and addressing YP's psychological/social well-being during their transition to adult services. Key Points • A wide range of psychological and social factors may be associated with how ready young people with juvenile idiopathic arthritis feel to move from paediatric to adult rheumatology services. • Transition outcomes may be improved by comprehensively assessing and addressing young people's psychological and social well-being.

Safety of the BNT162b2 mRNA COVID-19 vaccine in children and adolescents with juvenile idiopathic arthritis: a tertiary-center early experience

BackgroundResearch on the COVID-19 vaccination in patients with underlying rheumatic disorders in pediatric age is lacking. We studied possible adverse events of the mRNA BNT162b2 vaccine against SARS-CoV-2 (Pfizer-BioNTech) in children and adolescents with juvenile idiopathic arthritis (JIA), and also if there is a risk of flaring of the underlying JIA. We reported 36 JIA patients aged 5–18 years old received 2 doses of the COVID-19 vaccine (72 doses). Patients were followed before and after vaccination, and any related adverse event was recorded. JIA disease activity was assessed using Juvenile Arthritis Disease Activity Score-10 (JADAS-10) before and after vaccination.ResultsAmong 72 doses of the vaccine received, local adverse events (AEs) were reported by majority of the patients (66.7%); most commonly reported local AE was pain at the site of injection. Systemic AEs were revealed by (65.3%), most commonly reported systemic AEs were tiredness, myalgia, and headache. Almost all the reported AE were mild to moderate and resolved within 1–2 days and were also more frequently noted after the second dose. No flaring of the underlying primary rheumatic disease after vaccination. No one of the study group revealed serious adverse events.ConclusionsThis is one of the early studies reporting that mRNA COVID-19 vaccine seems to be safe in children and adolescents with JIA. Almost all the reported adverse events were mild to moderate and transient. Also, no serious adverse events or flaring of the primary disease were reported.

Vitamin D Profile and Disease Activity of JIA During Pandemic Covid-19

Vitamin D (25-Hydroxyvitamin D3 [25(OH)D3]) has an important role in the immune system. This study aimed to assess the relationship between 25-Hydroxyvitamin D3 and disease activity in Indonesian children with Juvenile Idiopathic Arthritis (JIA) during pandemic Covid-19. A 12-week randomized control trial was undertaken at Saiful Anwar Hospital between June and September 2021. JIA patients are divided into two groups. The control group (CG), without supplementation, and the treatment group (TG) got a high dose of oral cholecalciferol 2000 IU/day. Serum levels of 25(OH)D3 were measured using an enzyme-linked immunosorbent assay (ELISA). Comparison between serum 25(OH)D3 levels and JIA subtypes, peripheral blood Creactive protein (CRP), erythrocyte sedimentation rate (ESR), and Juvenile Arthritis Disease Activity Score (JADAS-27 Score) were analyzed using SPSS. There was a significant increase in serum 25(OH)D3 levels in treatment group (mean: 27.38 ± 6.39 ng/ml vs 42.26 ± 10.95 ng/ml; P=0.000). The JADAS-27 score significantly decrease in treatment group (14.60 ± 4.04 vs 6.24 ± 1.96; p= 0.000). Serum 25(OH)D3 showed a significant correlation with the JADAS-27 score. The levels of 25(OH)D3 are significantly decreased in children with JIA. Decreased 25(OH)D3 levels may be associated with the etiopathogenesis of JIA. Vitamin D levels have correlations with disease activity. Adjunctive treatment of cholecalciferol improves the disease activity in JIA patients. Keywords: Disease activity, JIA, Pandemic Covid-19, Vitamin D

Can ultrasound help to overcome uncertainty in clinical joint assessment in juvenile idiopathic arthritis?

Assessment of active synovitis is crucial for the management of juvenile idiopathic arthritis (JIA). We aimed to investigate the correlation of musculoskeletal ultrasound (MSUS) and clinical examination results and relate them to arthritis relapse rate. JIA patients with questionable presence of active arthritis (Q-joints) and controls (JIA and healthy children) were recruited. MSUS of Q-joints, active joints and their inactive counterparts was performed at study entry. Standard disease activity parameters were prospectively recorded. Of 481 joints of 138 JIA patients, 99 joints (20.6%) of 58 patients had one or more Q-joints with 54/99 (54.5%) having MSUS features of active disease. Clinically inactive joints had lower proportion of MSUS synovitis (78/253, 30.8%) while MSUS activity was present in 114/129 (88.4%) of clinically active joints and in 2/105 (1.9%) joints of 36 healthy controls. Within the 15-month follow-up 23/99 (22%) Q-joints and 31/253 (12%) clinically inactive joints relapsed. Joints with subclinical synovitis relapsed more frequently than MSUS inactive ones (p<0.001). The relapse rate was higher in MSUS-active Q-joints (19/23, 82%) than in clinically inactive ones (16/31, 52%) with MSUS synovial hypertrophy as the main relapse predictor in multivariate analysis. Ankle and knee joints relapsed most frequently. Acknowledgement of joints with questionable synovitis may contribute to the assessment of disease activity in JIA. Presence of MSUS synovitis carries a clinically meaningful risk of disease recurrence in these joints. In clinical practice, our findings encourage timely MSUS assessment of the joints in question, especially in patients without any other features of active disease.

Synovial signal intensity on static contrast-enhanced MRI for evaluation of disease activity in juvenile idiopathic arthritis – A look at the bright side of the knee

BackgroundKnowledge on the role of synovial signal intensity (SI) grading on static contrast-enhanced (CE) MRI of the knee for assessment of disease activity in juvenile idiopathic arthritis (JIA) is lacking. ObjectivesTo assess the value of synovial SI on static CE-MRI of the knee for evaluation of disease activity in children with JIA. Materials and methodsChildren with clinically inactive and clinically active JIA who underwent static CE-MRI of the knee were included. Synovial SI was evaluated on post-contrast T1-weighted fat-saturated images using a 0.02 cm2 region of interest drawn in the area of the synovium that contained visually the highest SI. To control for potential time-dependent post-contrast enhancement variability, a ratio between the SI of the synovium to the musculus gastrocnemius was calculated. ResultsWe included 427 JIA patients (clinically inactive JIA: 150 [35,1%]; clinically active JIA: 277 [64.9%]), 65.3% female, with a mean age of 13.3 ± 3.2 years. Mean SI synovium-to-muscle ratio was 2.1 ± 0.7 in patients with clinically inactive JIA versus 2.2 ± 0.8 in patients with clinically active JIA. Subgroup analysis showed no significant difference in SI synovium-to-muscle ratio between JIA patients with clinically inactive disease and JIA patients with clinically active disease (p-value 0.22). ConclusionsEvaluation of the brightness of the synovium on static CE-MRI of the knee for assessment of JIA disease activity should be avoided, as this might lead to incorrect clinical conclusions.