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Background: Juvenile idiopathic arthritis (JIA) is common in pediatric rheumatology. Despite treatment, many patients experience persistent disease activity. Joint hypermobility (JH), defined by an excessive range of motion across multiple joints, is prevalent in children and adolescents and may influence disease outcomes in JIA. Objective: This study examines the impact of JH on symptoms in youth and young adults with JIA. Methods: Data were obtained from the PR-COIN network and included patients under 21 years old with a diagnosis of JIA. Patients with JIA and JH were matched with those having JIA-only based on age, sex assigned at birth, JIA subtype, and medication exposure. Clinical data, including disease activity measures, patient well-being, and pain ratings, were collected at baseline and follow-up visits. Results: The sample included 420 patients with JIA + JH and 2100 with JIA only. The JIA + JH group exhibited higher disease activity at baseline, more active arthritis joints, elevated physician global assessment of disease activity scores, and worse patient-reported well-being. These differences persisted over time. The JIA + JH group had a 19–20% greater likelihood of maintaining high disease activity scores and worsening over subsequent visits, indicating a significant impact of JH on disease progression. Conclusion: JH in youth with JIA is associated with higher and persistent disease activity, suggesting that JH significantly contributes to the disease burden in patients with JIA and should be considered in treatment strategies. Future research should further explore the mechanisms by which JH influences disease activity and investigate comprehensive management approaches to improve outcomes for this population. Key Points • Children with JIA and joint hypermobility (JH) exhibit significantly higher disease activity at baseline compared to those with JIA only, including more active arthritis joints and elevated physician global assessment scores. • The presence of JH in JIA patients is associated with poorer patient-reported well-being and higher overall disease activity scores, which persist over time despite treatment. • JIA + JH patients have a 19–20% greater likelihood of maintaining high disease activity and worsening over subsequent visits, indicating a significant impact of JH on disease progression. • The study suggests that JH should be considered an important clinical factor in the management of JIA, with targeted interventions needed to address the increased disease activity and improve overall patient outcomes. [ABSTRACT FROM AUTHOR]

Objectives: Given the limited tocilizumab (TCZ) treatment data for systemic juvenile idiopathic arthritis (sJIA) in China, we evaluated the long-term efficacy and safety of TCZ in Chinese patients with sJIA. Method: In this multicentre, interventional Phase IV study, patients with sJIA and inadequate clinical response to non-steroidal anti-inflammatory drugs/corticosteroids received TCZ infusions every 2 weeks based on body weight (< 30 kg, 12 mg/kg; ≥ 30 kg, 8 mg/kg), over a 52-week open-label period and an 8-week safety follow-up period. The primary endpoint was the proportion of patients with a JIA American College of Rheumatology (ACR) 30 response and absence of fever at Week 12. Results: Sixty-two patients were enrolled and treated (12-mg/kg group, 34; 8-mg/kg group, 28). At Week 12, 87.1% (95% confidence interval 78.8%–95.4%) of patients had JIA ACR 30 response and absence of fever; Week 52 results were similar. The proportion of JIA ACR 30/50/70/90 responders rapidly increased at Week 12, up to Week 52. High-sensitivity C-reactive protein (hsCRP) levels decreased within 4 weeks; 44/58 patients (75.9%) with elevated baseline hsCRP recovered at Week 52. Childhood Health Assessment Questionnaire pain scores, disability index scores, and mean corticosteroid dose decreased over time. Height standard deviation score changes at Week 52 indicated catch-up growth. Most adverse events (AEs) were mild (serious AE incidence, 17.7%). No deaths or macrophage activation syndrome occurred. Conclusion: This is the first multicentre trial to report the efficacy and safety of TCZ in Chinese patients with sJIA at 52 weeks. No new safety concerns were found. Key points • This is the first multicentre trial providing strong evidence for tocilizumab (TCZ) treatment for systemic juvenile idiopathic arthritis (sJIA) in China. • The study reported TCZ had good efficacy and favourable safety profiles in Chinese sJIA patients in the long term (52 weeks). • TCZ treatment showed rapid disease control, which was maintained over time, catch-up growth benefits in patients, tapering and discontinuation of corticosteroids, and improved quality of life. [ABSTRACT FROM AUTHOR]

Objective: This study aims to assess current diagnostic and management for systemic Juvenile Idiopathic Arthritis (sJIA) among physicians, evaluate the challenges encountered in diagnosis and treatment, and identify the educational needs and professional development engagements of physicians managing sJIA. Methods: A nationwide survey was conducted from November 2023 to March 2024 across tertiary and secondary pediatric and general hospitals in China. The survey targeted physicians with at least three years of specialty experience, resulting in 310 valid responses from 25 provinces, autonomous regions, and municipalities. The survey collected data on diagnostic practices, treatment approaches, and professional development related to sJIA. Data collection was facilitated through WeChat, and statistical analysis was performed using descriptive statistics. Ethical approval was obtained from the Ethics Committee of Beijing Children's Hospital, with informed consent provided electronically by participants. Results: The survey indicated that all physicians encountered suspected or confirmed cases of sJIA, highlighting its prevalence and the diagnostic challenges associated. Regarding diagnostic standards, 53.9% of physicians used the "Consensus on the Diagnosis and Treatment of sJIA and Macrophage Activation Syndrome," 18.1% followed the International League of Associations for Rheumatology (ILAR) standards, and 24.8% adhered to the Pediatric Rheumatology International Trials Organization (PRINTO) standards. In treatment strategies, glucocorticoids and IL-6 receptor monoclonal antibodies were extensively used, with the latter receiving "excellent" and "satisfactory" ratings of 46.5% and 36.1%, respectively, demonstrating high efficacy and acceptance. Main challenges included high treatment costs, complexity of diagnosis, patient compliance issues, and potential long-term side effects of biologics. Additionally, 126 doctors (40.7%) actively participated in more than three academic conferences or systematic learning courses related to sJIA, indicating a strong demand for ongoing education, particularly in new treatment developments and diagnostic skills. Conclusion: The findings emphasize the necessity for standardized diagnosis and customized treatment plans tailored to patient-specific conditions in managing sJIA. Key Points • The survey highlights the prevalence and clinical challenges of sJIA among physicians, emphasizing the importance of vigilant diagnosis, multi-system involvement, and differential diagnosis to improve treatment outcomes and patient quality of life. [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: The objective of this study is to investigate extraarticular manifestations (EAMs) in patients with juvenile idiopathic arthritis (JIA) and assess their impact on health-related quality of life (HRQoL) among these patients. Methods: This cross-sectional analytic study was carried out on 117 patients with JIA. EAMs were identified clinically by history and examination. Sicca symptoms, peripheral neuropathy, enthesitis, and skin lesions were picked up during clinical examination. Pulmonary involvement was evaluated by high-resolution CT chest. Patients were assessed by abdominal ultrasonography to assess the size of liver and spleen. Atlantoaxial subluxation was evaluated by cervical spine x-rays. Patients were evaluated by Pediatric Quality of Life Inventory-4 (PedsQL-4) and PedsQL-3 arthritis module. Results: The median age of patients was 14 years with a median disease duration 4 years, 82.9% were females. Of the studied 117 JIA patients, 85 patients (72.6%) had at least one EAM. Persistent fatigue (51.3%) was the most prevalent EAM, followed by recurrent skin rash (16.2%), enthesitis (15.4%), recurrent fever (13.7%), and uveitis (12%). Patients with EAMs scored significantly lower in physical functioning (p = 0.001), emotional functioning (p < 0.001), social functioning (p = 0.005), and school functioning (p = 0.001). Regarding PedsQL arthritis module, patients with EAM had also significantly lower scores than did patients without EAM on the domains of pain and hurt (p < 0.001), daily activities (p = 0.008), and worry (p = 0.001). Results: EAMs are prevalent among JIA patients and have a negative impact on their HRQoL. So, early identification and treatment are highly recommended. Key Points • A large percentage of JIA patients experienced at least one extraarticular manifestation (EAM). • Persistent fatigue and recurrent skin rash are the most prevalent EAMs in JIA patients. • JIA patients with EAMs have worse scores in almost all domains of HRQoL. [ABSTRACT FROM AUTHOR]

Objective: To determine the dynamics of serum levels of TNF-α in patients with juvenile idiopathic arthritis (JIA) treated with anti-TNF-α biological drugs and investigate their association with the disease activity. Methods: We conducted a single-centre, observational cohort study in 98 patients with JIA (30 boys, 68 girls, mean age 11.3 years) treated with anti-TNF-α biological drugs. Clinical examinations and laboratory assessments of serum levels of TNF-α were performed before starting therapy with biological drug and at 6-month intervals afterwards up to 2.5 years. Results: The analysis of serum levels of TNF-α in relation to the disease activity states showed the highest mean serum levels of TNF-α in patients on etanercept who had low disease activity states and in patients on adalimumab who had inactive disease. The correlation analysis in patients with JIA treated with etanercept or adalimumab showed a weak negative correlation between the serum levels of TNF-α and JADAS10 scores (p = 0.007), (r = − 0.177). Conclusion: The assessment of serum levels of TNF-α in children with JIA during treatment with etanercept or adalimumab is not a reliable biomarker of disease activity or immunological remission. Longitudinal measurement of TNF-α has no added clinical value in patients with JIA treated with anti-TNF-α biological drugs. Key Points • There is limited evidence regarding the effect of anti-TNF therapy on serum concentrations of TNF-α in patients with juvenile idiopathic arthritis • Our study showed an increase in the serum level of TNF-α after the initiation of therapy with either etanercept or adalimumab, which was more significant in patients with inactive or low disease activity • Serum TNF-α is most likely not biologically active during therapy with TNF-α inhibitors and therefore not a reliable biomarker of disease activity or immunological remission in patients with juvenile idiopathic arthritis [ABSTRACT FROM AUTHOR]

Juvenile Idiopathic Arthritis (JIA) causes caregiver burden on families with children affected with it. Our study aimed to explore this multifaceted burden in the Indian context. In this cross-sectional study, we administered the Hindi translated CAREGIVER questionnaire to adult caregivers in the families of JIA patients ≤ 18 years. The responses to the 28 items were used to calculate the burden scores in various dimensions. The relationship of the global burden scores with demographic and socioeconomic factors were analysed. Non parametric tests were used. Two hundred twenty-one caregivers participated with a median age of 39 years (IQR 32–45). This included 116 fathers, 50 mothers, 32 brothers, 18 uncles, three grandfathers, one sister, and one grandmother. The JIA patients had a median age of 15 (12–17) years, and the male-to-female ratio was 3.2:1. Enthesitis-related arthritis was the predominant subtype (72.4%). Most caregivers (70.6%) expressed sadness at diagnosis, and 29.9% continued to express sadness. Nearly two-thirds (65.6%) had to borrow money from others. More than half (59.3%) of the caregivers neglected their health, and 9.0% became sick. Male gender of the child, systemic JIA subtype, low socioeconomic status, high disease activity, extra-articular damage, high parent-reported disease activity and poor quality of life were associated with higher global caregiver burden. JIA has a significant emotional, social, economic, and labour impact on caregivers. Economic and psychosocial support needs to be given to family caregivers caring for children with JIA. Key Points • JIA causes a chronic emotional toll on caregivers, which is aggravated by high disease activity in the child. • Caregivers from rural areas and lower socioeconomic groups face disproportionate economic burden, often aggravated by losing jobs due to caregiving responsibility. • The use of biologics was low despite high disease activity, highlighting the need for financial support. • Parent-reported outcome measures significantly correlated with caregiver burden, underscoring the importance of integrating family perspectives in care. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to assess the cultural adaptation, validity, and reliability of the Turkish version of the Juvenile Arthritis Quality of Life Questionnaire (JAQQ) in patients with juvenile idiopathic arthritis (JIA). Methods: A total of 100 JIA patients (64% female), aged 9 to 18 years, participated in the study conducted at a tertiary care university hospital. The JAQQ was culturally adapted through a rigorous translation process and administered alongside established measures, including the Childhood Health Assessment Questionnaire (CHAQ), Juvenile Arthritis Biopsychosocial Questionnaire (JABQ), and Children's Depression Inventory (CDI). Validity and reliability were evaluated using Spearman's correlation coefficients, Cronbach's alpha, intraclass correlation coefficient (ICC), standard error of the mean (SEM), and minimal detectable change (MDC). Results: The Turkish version of JAQQ exhibited high convergent validity, correlating significantly with CHAQ, JABQ, and CDI. No floor or ceiling effects were observed in the total JAQQ score, indicating a balanced assessment. Internal consistency was excellent (Cronbach's α = 0.948), and test–retest reliability was satisfactory (ICC = 0.913). SEM and MDC95 values were 0.357 and 0.99, respectively. Conclusions: The Turkish adaptation of JAQQ emerges as a valid and reliable instrument for comprehensively assessing the health-related quality of life in children and adolescents diagnosed with JIA. The questionnaire's robust psychometric properties, coupled with distinctive features like individualized assessment, highlight its potential as a valuable tool for both clinical assessment and scientific research in the field of pediatric rheumatology. Key Points • The Juvenile Arthritis Quality of Life Questionnaire (JAQQ) is an important scale that evaluates the quality of life of children with Juvenile Idiopathic Arthritis (JIA). • JAQQ is known and used in the field of pediatric rheumatology in Turkey, but its Turkish adaptation has not been made before. • Our study includes 100 JIA patients aged between 9 and 18 years and shows that the Turkish version of JAQQ is valid and reliable in measuring the quality of life of these children. • This research contributes to the accurate assessment of the quality of life in Turkish children diagnosed with JIA, providing valuable insights for both clinical and scientific studies. [ABSTRACT FROM AUTHOR]

Objective: 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. Methods: 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. Results: 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 (> 1.1 mg/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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to assess the prevalence and identify predictors of hepatic steatosis and fibrosis in patients with juvenile idiopathic arthritis (JIA) during methotrexate treatment. Method: This cross-sectional study included JIA patients who had received methotrexate for > 1 year. Laboratory data including liver chemistry and lipid profiles were collected. Liver stiffness measurements (LSM) and controlled attenuation parameters (CAP) were determined by transient elastography. Significant hepatic fibrosis was defined as LSM > 7 kilopascal (kPa), and hepatic steatosis was defined as CAP > 225 decibel/meter (dB/m). Logistic regression analysis was performed to identify predictors associated with hepatic steatosis and fibrosis. Results: Of 60 patients, 66.7% were female, and the median age (IQR) was 12.8 (10.6–15.0) years. The median duration of methotrexate usage (IQR) was 45 (22–85) months, and the median cumulative dose of methotrexate (IQR) was 3768 (1806–6466) mg. The median LSM (IQR) and CAP (IQR) were 4.1 (3.4–4.6) kPa and 191.0 (170.3–223.8) dB/m, respectively. No patients had transient elastography-defined hepatic fibrosis, whereas 21.7% had hepatic steatosis. A body mass index Z-score > 1 (OR 5.71 [95%CI 1.31–24.98], p = 0.021) and higher cumulative dose of methotrexate (OR 1.02 [95%CI 1.00–1.04], p = 0.041) were associated with hepatic steatosis, whereas the cumulative dose of steroids was not (OR 1.00 [95%CI 1.00–1.01], p = 0.097). Conclusions: Hepatic steatosis is common among JIA patients receiving methotrexate, but none had transient elastography-defined hepatic fibrosis. Overweight/obese JIA adolescents and patients with a high cumulative dose of methotrexate are at risk for hepatic steatosis. Key Points •Long-term low-dose methotrexate usage and the concomitant use of other DMARDs did not increase the risk of hepatic fibrosis in JIA patients. •The prevalence of hepatic steatosis in JIA patients receiving methotrexate was higher than in a healthy pediatric population. •Overweight/obesity and a higher cumulative dose of methotrexate were predictors of hepatic steatosis. [ABSTRACT FROM AUTHOR]

Objectives: Macrophage activation syndrome (MAS) is a severe complication of systemic juvenile idiopathic arthritis (SJIA). We aimed to compare the characteristics of SJIA patients who developed MAS in the disease course to those who never experienced MAS. Methods: Patients with SJIA were included. The features of the patients at the time of SJIA diagnosis were compared. Multivariate logistic regression and ROC analyses were used while evaluating factors associated with MAS. Results: Overall, 126 SJIA patients (M/F:1.17) were included. Eighty-six (68.2%) never had MAS. At the time of SJIA diagnosis, age was younger; the duration of fever was longer; rash, hepatomegaly, and splenomegaly were more frequent and arthralgia/arthritis was less common among patients who had MAS in the follow-up than those who never had MAS. Also, white blood cell, neutrophil, and platelet counts and fibrinogen were lower, while transaminases, lactate dehydrogenase, triglyceride (TG), and ferritin levels were higher among patients with MAS than those without MAS. The multivariate regression analysis disclosed age at symptom onset, duration of fever, platelet count, TG and ferritin levels as independent MAS predictors. For ferritin level/platelet count (F/P) ratio at the time of SJIA diagnosis, a threshold of ≥1.1 performed best to predict a MAS-prone disease course with a sensitivity of 90% and a specificity of 82.6%. Conclusion: The F/P ratio at the time of SJIA diagnosis may be a promising biomarker to predict MAS-prone disease course in SJIA. Determining MAS-prone patients at the time of SJIA diagnosis could assist physicians while tailoring SJIA treatment individually. Key points • Systemic juvenile idiopathic arthritis (SJIA) patients with macrophage activation syndrome (MAS) differ from SJIA patients who never have MAS, at the time of SJIA diagnosis. • It could be possible to predict a MAS-prone disease course at the time of SJIA diagnosis. • The ferritin/platelet ratio is a promising biomarker for predicting MAS-prone SJIA disease course. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to investigate the frequency and type of FMF-associated inflammatory diseases in a large FMF pediatric patients and to compare them to those FMF patients without concomitant inflammatory diseases. Materials and methods: Familial Mediterranean fever patients enrolled in the Pediatric Rheumatology Academy (PeRA)-Research Group (RG) were included. The patients were divided into two groups according to concomitant inflammatory disease as FMF patients who had a concomitant inflammatory disease (group 1) and FMF patients who did not have a concomitant inflammatory disease (group 1). The clinical findings and treatments were compared between the two groups. Results: The study group comprised 3475 patients with FMF. There were 294 patients (8.5%) in group 1 and 3181 patients (91.5%) in group 2. Juvenile idiopathic arthritis (n = 136) was the most common accompanying inflammatory disease. Arthritis, M694V homozygosity, and the need for biological therapy were more frequently observed in Group 1 (p < 0.05). Fever and abdominal pain were more frequently detected in Group 2 (p < 0.05). FMF patients with concomitant inflammatory diseas more frequently demonstrated colchicine resistance. There were no significant differences in the median attack frequency, chest pain, amyloidosis, erysipelas-like erythema, or family history of FMF between the two patient groups. Conclusion: To the best of our knowledge, this is the largest pediatric cohort reviewed to date. FMF patients may have different clinical profiles and colchicine responses if they have with concomitant inflammatory diseases. Key points • FMF is associated with some inflammatory comorbidities diseases. • To the best of our knowledge, this is the largest cohort evlauated pediatric FMF associated inflammatory comorbidities diseases reviewed to date [ABSTRACT FROM AUTHOR]

Background: Juvenile idiopathic arthritis (JIA) is a chronic rheumatic disease that affects children. It is crucial to detect and treat hip involvement in JIA early to prevent functional impairment and reduced quality of life. The Childhood Arthritis Radiographic Score of the Hip (CARSH) is a validated radiographic scoring system used to assess hip involvement in JIA. In this study, we aimed to determine cut-off values for CARSH scores using cluster analysis. Methods: The study was conducted as a cross-sectional analysis and included JIA patients with hip involvement who underwent a pelvic radiograph. The same pelvic radiograph was interpreted by two experienced pediatric rheumatologists at baseline and after 3 weeks by both readers for reliability. The CARSH scores were calculated for each hip four times (twice by each reader). For the 50 hips, a total of 200 interpretations of the CARSH score were obtained. Model-based clustering was employed to identify distinct groups of CARSH score interpretations and characterize the phenotype of each cluster. Results: Twenty-five children with hip involvement were included. The mean age was 13.9 ± 4.6 years. JIA subtypes were as follows: ERA in 64%, oligoarthritis in 16%, psoriatic arthritis in 12%, polyarthritis RF + in 4%, and RF − in 4% of patients. For the 200 hip interpretations, three clusters based on the level of the CARSH were identified by model-based clustering. Cluster 1 consisted of 17 CARSH score interpretations with a median score of 7 ± 3 (ranging from 1 to 15). This group primarily comprised patients with enthesitis-related arthritis (ERA) and psoriatic arthritis. Patients in cluster 1 were generally older, experienced longer diagnostic delays, and had a longer disease duration compared to the other clusters. Cluster 2 exhibited a moderate CARSH score, with an average score of 4 ± 3 (1 to 15). Patients in this group had significantly higher body weight compared to the other clusters. Cluster 3 represented the group with the least severe hip involvement, characterized by CARSH scores of 2 ± 1 (ranging from 0 to 9). This cluster had a higher proportion of male patients and higher C-reactive protein (CRP) levels than the other clusters. Regarding the individual items of the CARSH score, cluster 1 showed higher percentages of hip radiograph abnormalities such as joint space narrowing, erosions, growth abnormalities, and subchondral cysts. Cluster 2 was characterized by a high rate of acetabular sclerosis, with little to no abnormalities in other CARSH score items. Cluster 3 was the only group that exhibited hip subluxation, with minimal abnormalities in the other score items. In conclusion, this study identified three distinct groups of CARSH scores, representing varying levels of severity in hip involvement in JIA. These findings provide valuable insights for clinicians in assessing and managing JIA patients with hip involvement, enabling tailored treatment strategies based on the severity of the condition. Key Points • While a Childhood Arthritis Radiographic Score of the Hip (CARSH) is a valid and reliable tool in hip-related juvenile idiopathic arthritis, its use is limited in daily practice due to the lack of available cut-off values. • The cluster analysis defined three clusters based on the CARSH levels. • Cluster 1 exhibited the highest score with more damage and disability. Cluster 2 involved a moderate score and more overweight patients. Cluster 3 included the least level of the score but with an active disease parameter. [ABSTRACT FROM AUTHOR]

Background/Objectives: The aim of the study is to assess the effect of juvenile idiopathic arthritis (JIA) and biologic disease-modifying anti-rheumatic drugs (bDMARDs) on ovarian reserve in children. Materials and Methods: A cross-sectional study was performed from March 2021 to March 2022 and included 81 patients with JIA and 49 healthy children. Serum anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol levels were analyzed using electrochemiluminescence methods. Results: The mean of current age (13.5 ± 3.2 vs. 14.4 ± 2.4 years), height standard deviation score (SDS) (− 0.35 ± 1.18 vs. − 0.44 ± 0.94), body mass index SDS (0.12 ± 1.33 vs. 0.25 ± 1.28), and the median weight SDS (− 0.13 (− 2.27–3.23) vs. − 0.52 (− 3.4–3.3)) were similar in JIA patients and controls (p > 0.05). Patients with JIA were divided into two groups according to their treatment regimens: treated with methotrexate (MTX) (biologic naive) (n = 32) and treated with MTX plus bDMARDs (n = 49). No significant differences were detected between the 3 groups regarding menarche age, menstrual cycle length, and flow duration (for all p > 0.05). The median serum concentration of AMH was 2.94 (1.12–7.88) ng/ml in the control group, 3.02 (0.36–8.54) ng/ml in the biologic naïve group, and 3.01 (0.99–8.26) ng/ml in the MTX plus bDMARD group. There were no significant differences between 3 groups according to serum AMH, FSH, LH, and estradiol levels (p > 0.05). Conclusion: Biologic DMARDs are reassuring in terms of ovarian reserve in girls with JIA and demonstrate that AMH is unaffected by treatment. Prospective studies with larger sample sizes are needed to confirm our findings and to evaluate the impact on the future fertility of patients. Key Points • Although biologic disease-modifying anti-rheumatic drugs (bDMARDs) are being game-changing treatment options in juvenile idiopathic arthritis, their effect on fertility and ovarian reserve is one of the most discussed issues. • In addition to treatment used, autoimmune diseases might also have a negative effect on fertility. • In this cross-sectional study, we found that anti-Mullerian hormone level of patients who were on bDMARDs, patients who were on methotrexate, and healthy controls were similar. • Our results suggest that bDMARDs are reassuring in terms of ovarian reserve in girls with JIA and demonstrate that AMH is unaffected by treatment. [ABSTRACT FROM AUTHOR]

Subclinical synovitis is highly prevalent in patients with JIA in clinical remission (CR) with a short duration. The objective was to evaluate its prevalence by ultrasound (US) in patients with JIA in long CR during a one-year follow-up. In this prospective and longitudinal study, we included 76 patients with JIA according to ILAR with CR by the Wallace modified criteria and JADAS27 and compared them with 22 patients with active disease. Clinical and demographic characteristics were recorded. US evaluation was by 10-joint count. Differences in US evaluations were analyzed by the Mann–Whitney U test. There were no differences among the two group with regard to disease duration at enrollment, and age (p = 0.540 and p = 0.080, respectively), but JADAS 27, CHAQ, and acute phase reactants were significantly higher (p < 0.001) in the clinically active group. The prevalence of subclinical synovitis at baseline and the end of the study in the CR group was 18.4% and 11.8%, respectively, while it was 100% and 40.9% in the active disease group. Subclinical synovitis at baseline was significantly more prevalent in the clinically active group (elbow, p = 0.01; wrist, p = 0.001; MCP 2, p = 0.001; knee, p = 0.001 and ankle p = 0.001; and PD only in the ankle, p = 0.002). The concordance of inter-reader reliability in all evaluated joints was excellent (p = 0.001). Although the prevalence of subclinical synovitis is low in patients with JIA with long-term clinical remission on medication, a percentage of patients continue to have subclinical involvement that could predict the risk of relapse and structural damage. Key Points • Subclinical synovitis is less prevalent in JIA in long-term clinical remission compared to patients in short-term remission. • The persistence of imaging signs of inflammation in a significant percentage of patients may indicate the need for ongoing medication. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study of children with juvenile idiopathic arthritis (JIA) was to use proton magnetic resonance spectroscopy (1H-MRS) to compare the levels of five neurometabolites in the right and left insular cortexes of subjects in three groups: JIA-active, JIA-inactive, and healthy controls (HCs). Methods: Two inflammation markers and five psychometric scores were determined. 1H-MRS was used to measure the levels of total N-acetylaspartate (NAA), total choline (Cho), myo-inositol (mI), and glutamate (Glu), and the complex of glutamine and glutamate (Glx) relative to total creatine (tCr) in the right and left insular cortexes of participants. Results: Intra-group comparisons indicated that each group had higher levels of NAA/tCr, Glu/tCr, Glx/tCr, and mI/tCr in the right insula, and higher levels of Cho/tCr in the left insula. Inter-group comparisons of the right insula indicated that the JIA-active and JIA-inactive groups had higher levels of Cho/tCr than the HC group, but none of the other inter-group differences were statistically significant. The score of the Sleep Disturbance Scale for Children (SDCD) had an inverse correlation with the level of Cho/tCr in the right insular cortex of patients in the JIA-inactive group. Conclusions: Relative to the HC group, the right insular cortex of subjects in the JIA-active and the JIA-inactive groups had greater levels of Cho/tCr, suggesting increased inflammation in this region. The Cho/tCr level in the right insular cortex had an inverse correlation with SDCD score in the JIA-inactive group. Key Points • Healthy controls and JIA patients had higher levels of tNAA/tCr, Glu/tCr, Glx/tCr, and mI/tCr in the right insula, and higher levels of Cho/tCr in the left insula. • A greater level of Cho/tCr in the right insula of JIA-active and JIA-inactive patients indicated neuroinflammation in this region. • The Cho/tCr level in the right insular cortex had an inverse correlation with SDCD score in the JIA-inactive group. [ABSTRACT FROM AUTHOR]

Objectives: Care for JIA patients has been transformed in the biologics era; however, biologics carry important (although rare) risks and are costly. Flares after biological withdrawal are seen frequently, yet there is little clinical guidance to identify which patients in clinical remission can safely have their biologic discontinued (by stopping or tapering). We examined what characteristics of the child or their context are important to pediatric rheumatologists when making the decision to discuss withdrawal of biologics. Methods: We conducted a survey including a best-worst scaling (BWS) exercise in pediatric rheumatologists who are part of the UCAN CAN-DU network to assess the relative importance of 14 previously identified characteristics. A balanced incomplete block design was used to generate choice tasks. Respondents evaluated 14 choice sets of 5 characteristics of a child with JIA and identified for each set which was the most and least important in the decision to offer withdrawal. Results were analyzed using conditional logit regression. Results: Fifty-one (out of 79) pediatric rheumatologists participated (response rate 65%). The three most important characteristics were how challenging it was to achieve remission, history of established joint damage, and time spent in remission. The three least important characteristics were history of temporomandibular joint involvement, accessibility of biologics, and the patient's age. Conclusions: These findings give quantitative insight about factors important to pediatric rheumatologists' decision-making about biologic withdrawal. In addition to high quality clinical evidence, further research is needed to understand the perspective of patients and families to inform shared decision-making about biologic withdrawal for JIA patients with clinically inactive disease. Key Points ● What is already known on this topic—there is limited clinical guidance for pediatric rheumatologists in making decisions about biologic withdrawal for patients with juvenile idiopathic arthritis who are in clinical remission. ● What this study adds—this study quantitatively examined what characteristic of the child in clinical remission, or of their context, are most important to pediatric rheumatologists in deciding whether to offer withdrawal of biologics. ● How this study might affect research, practice or policy—understanding of these characteristics can provide useful information to other pediatric rheumatologists in making their decisions, and may guide areas to focus on for future research. [ABSTRACT FROM AUTHOR]

Objectives: The objectives were to explore the response to intraarticular triamcinolone acetonide (TA) injection in children with non-systemic juvenile idiopathic arthritis (JIA) and factors associated with time to arthritis flare. Methods: This was a retrospective cohort study of children with non-systemic JIA who received intraarticular TA injections at a tertiary care hospital in Bangkok, Thailand. Response to intraarticular TA injection was defined as absence of arthritis at 6 months after procedure. Time from joint injection to arthritis flare was recorded. Kaplan–Meier survival analysis with logarithmic rank test and multivariable Cox proportional hazards regression analysis were used for outcome analyses. Results: Intraarticular TA injection was performed in 177 joints among 45 children with non-systemic JIA, most common in the knees (57 joints, 32.2%). Response to intraarticular TA injection at 6 months was observed in 118 joints (66.7%). Ninety-seven joints (54.8%) had arthritis flare following injection. The median time to arthritis flare was 12.65 months (95%CI 8.20–17.10 months). The significant risk factor associated with arthritis flare was the JIA subtypes other than persistent oligoarthritis (HR 2.62, 95%CI 1.085–6.325, p = 0.032); the significant protective factor was concomitant sulfasalazine use (HR 0.326, 95%CI 0.109–0.971, p = 0.044). Adverse effects included pigmentary changes (3, 1.7%) and skin atrophy (2, 1.1%). Conclusion: Intraarticular TA injection in children with non-systemic JIA had favorable response in two thirds of injected joints at 6 months. The JIA subtypes other than persistent oligoarthritis was a predictor of arthritis flare following intraarticular TA injection. Key Points • Intraarticular TA injection in children with non-systemic JIA had a favorable response in two-thirds of injected joints at 6 months. • The median time from intraarticular TA injection to arthritis flare was 12.65 months. • The risk factor predicting arthritis flare was the JIA subtypes other than persistent oligoarthritis (extended oligoarthritis, polyarthritis, ERA, and undifferentiated JIA), while the concomitant use of sulfasalazine was a protective factor. • Local adverse reactions from intraarticular TA injection were less than 2% of injected joints. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed at evaluating the effect of genicular nerve block (GNB) in juvenile idiopathic arthritis (JIA) patients with persistent unilateral knee arthritis on pain, inflammatory parameters, function, and range of motion. Methods: A total of 104 JIA patients were diagnosed according to the International League Against Rheumatism (ILAR) criteria with persistent unilateral knee arthritis. They were allocated randomly into 2 groups: group 1 treated with GNB, while group 2 was treated with intra-articular triamcinolone (TA) only. Visual analogue scale (VAS) on pain, sonography of large joints in rheumatology (SOLAR) scoring system, and Lysholm scores were assessed at 0-, 2-, and 12-week intervals. Swelling and tenderness were clinically evaluated semi-quantitatively (0-3) at the same time intervals. Results: VAS pain, tenderness, swelling, and SOLAR grey scale (GS) and power Doppler (PD) scores were significantly reduced after 2 weeks in both groups (p < 0.05). This was greater in the GNB group regarding VAS and tenderness, while SOLAR and swelling were stronger reduced in TA group. After 12 weeks, all outcome measures showed lower values in the GNB group compared to TA, and this was significant regarding VAS pain. Moreover, Lysholm functional score was significantly increased in both groups at both intervals; and higher values were seen in the TA group compared to GNB after 2 weeks. Conclusion: GNB was able to control pain and improve function and inflammation of the knee joint in JIA patients. Though steroid attained better results after 2 weeks, GNB achieved an equivalent longer-term improvement after 12 weeks. Trial registration identifying number: NCT04687930. Key Points • Persistent knee arthritis treatment in JIA is always challenging. • GNB was approved for treatment of pain in knee osteoarthritis. • GNB in the present study succeeded to control active knee arthritis and this effect was comparable to intra-articular steroid injection. [ABSTRACT FROM AUTHOR]

Hyperimmunoglobulin D syndrome (HIDS) is a hereditary autoinflammatory disease characterized by recurrent inflammatory attacks with fever, abdominal pain, lymphadenopathy, aphthous stomatitis, and skin lesions. There are few reports on HIDS patients complicated with macrophage activation syndrome (MAS); however, to our knowledge, there is no case of HIDS with recurrent MAS attacks. We report two pediatric patients initially diagnosed as Kawasaki disease and systemic juvenile idiopathic arthritis presented with recurrent MAS episodes with prolonged fever, skin rash, hepatosplenomegaly, cervical lymphadenopathy, aphthous stomatitis, headache, pancytopenia, hyperferritinemia, and hypofibrinogenemia, finally diagnosed as HIDS with a documented homozygous MVK gene mutation. This is the first report on recurrent MAS attacks due to HIDS in pediatric patients who were successful treated with corticosteroids and anti-IL-1 therapies. Thus, clinicians should be vigilantly investigated signs of autoinflammatory diseases in patients with recurrent MAS attacks during their disease course, and HIDS should be considered an underlying disease for triggering recurrent MAS attacks. We have also reviewed the current literature regarding HIDS cases complicated with a MAS attack and summarized their demographic, treatment, and outcome characteristics. Key points • Hyperimmunoglobulin D syndrome should be considered in differential diagnosis in patients who experienced recurrent macrophage activation syndrome attacks. [ABSTRACT FROM AUTHOR]

Objectives: To compare the ability of the modified Systemic Manifestation Score (mSMS) and the mPouchot score to distinguish adult-onset Still's disease (AOSD) with high disease severity in a large cohort. Methods: We scored the disease severity of 174 patients and categorized them into high and low disease severity states. The correlation of mSMS and mPouchot score with ESR, CRP, ferritin, liver function tests, and serum cytokines was investigated. Receiver operator characteristic (ROC) curve and logistic regression analysis were performed to compare the ability of mSMS and mPouchot to distinguish patients with severe AOSD. Results: Both mSMS and mPouchot score were positively correlated with ESR (both P < 0.001), CRP (both P < 0.0001), and serum ferritin (both P < 0.0001). Moreover, both mSMS and mPouchot score are significantly associated with liver dysfunction and high IL-18 (both P < 0.0001) and IL-6 (both P < 0.01) levels in AOSD patients. Furthermore, the area under curve (AUC) value of mSMS was significantly less than of mPouchot score (0.71 for mSMS, 0.81 for mPouchot score, P < 0.0001). Compared with mPouchot score, mSMS had higher sensitivity (75.64% vs 74.36%) and lower specificity (55.06% vs 76.40%). And mSMS had a worse performance in assessing high disease severity than mPouchot score in logistic analysis. Conclusion: Both scores are proven as effective to assess disease severity of AOSD. By contrast, mSMS perform worse in assessing high disease severity of AOSD patients than mPouchot score. Key Points • Both modified Systemic Manifestation Score (mSMS) and modified Pouchot score (mPouchot score) positively correlated with ESR, CRP, and serum ferritin of AOSD patients. • Both scores are significantly associated with impaired liver function and high serum cytokine levels. • mSMS had lower discriminative ability than mPouchot score to distinguish high disease severity of AOSD patients. [ABSTRACT FROM AUTHOR]

Introduction: Intra-articular corticosteroid injection (IACI) is generally used in the management of juvenile idiopathic arthritis (JIA) to obtain rapid relief of active synovitis and functional recovery and to prevent the need for regular systemic therapy. The aim of this study was to investigate the outcome of IACI treatment and the factors associated with remission of synovitis. Methods: The clinical records of JIA patients who received IACI between January 2014 and December 2020 in two pediatric rheumatology centers were reviewed. The procedure was evaluated in terms of efficacy, factors that may affect the duration of remission, procedural and drug-related complications. Results: During the study period, 134 patients received 227 injections and 37 joints were injected more than once. One hundred and six (79%) patients had persistent oligoarticular disease. At the time of injection, all patients were receiving non-steroidal anti-inflammatory drugs, 74 patients were on methotrexate, and 14 patients were on biologics. The median duration of remission without exacerbation of synovitis treated with IACI was 15 (range 1–64) months. The inactivity rate was 81% at the 6th month after the injection. It has been shown that being less than 7 years old at disease onset and low initial CRP levels were correlated with a long remission period (p < 0.05). Despite the differences were not statistically significant, the duration of remission was longer in boys, in ANA positives, in HLA-B27 negatives, in patients with concurrent methotrexate treatment and in patients not receiving biologic therapy (p > 0.05). Only two patients (1.5%, 95% CI − 0.6 to 3.5) developed cutaneous hypopigmentation and subcutaneous atrophy as side effects of injection. Conclusion: Intra-articular corticosteroid injection was more effective especially in patients with low initial CRP levels and younger than 7 years of age. The duration of remission was longer in these patients. KeyPoints • Intra-articular corticosteroid injection is an effective method for controlling joint inflammation and achieving long-term remission without significant side effects. • Intra-articular corticosteroid injection can be preferred in all forms of juvenile idiopathic arthritis as primary therapy or to relieve the patient while waiting for the effect of systemic agents or to avoid increasing the dose of systemic drugs. • It can be recommended as a treatment option at any stage of the disease, especially in young patients and patients with low initial CRP values. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: The most frequent adverse events (AEs) of methotrexate (MTX) are gastrointestinal symptoms and hepatotoxicity, which can affect its adherence, leading to reduced effectiveness. The SLCO1B1 gene codes for a liver protein (OATP1B1) responsible for drug transportation. Genetic variations within the SLCO1B1 gene locus impact drug transport, leading to altered pharmacokinetic profiles, delayed MTX clearance, and increased risk of toxicity. This study aimed to determine the association between single nucleotide polymorphisms (SNPs) in the SLCO1B1 gene (rs4149056, rs2306283) with the development of AEs in patients with juvenile idiopathic arthritis (JIA) treated with MTX.We performed an observational retrospective study to analyze the relationship between SNPs in the SLCO1B1 gene and the development of AEs in pediatric patients treated with MTX for JIA.Thirty patients with JIA were included, 22 females (73.3%), with a median age of 11 years (IQR 8.3–15). The most frequent JIA subtype was rheumatoid factor-positive polyarthritis (36.7%). Twenty patients (66.7%) reported AEs. The *1B haplotype was the most frequent in this group (53.3%) and conferred a higher risk of developing AEs (OR = 3.89, 95% CI = 1.23 -12.29, p = 0.03).Patients with the allele *1B may benefit from lower doses of MTX. SLCO1B1 genotyping is a promising technique to identify patients at higher risk of AEs during treatment with MTX, thus requiring dose optimization.Key Points• The most frequent SLCO1B1 haplotype in our population was *1B, also associated with a higher risk of developing adverse events (OR=3.89, 95% CI=1.23 -12.29, p=0.03). • SLCO1B1 genotyping is a promising tool to help identify patients at higher risk of MTX-related AEs.Method: The most frequent adverse events (AEs) of methotrexate (MTX) are gastrointestinal symptoms and hepatotoxicity, which can affect its adherence, leading to reduced effectiveness. The SLCO1B1 gene codes for a liver protein (OATP1B1) responsible for drug transportation. Genetic variations within the SLCO1B1 gene locus impact drug transport, leading to altered pharmacokinetic profiles, delayed MTX clearance, and increased risk of toxicity. This study aimed to determine the association between single nucleotide polymorphisms (SNPs) in the SLCO1B1 gene (rs4149056, rs2306283) with the development of AEs in patients with juvenile idiopathic arthritis (JIA) treated with MTX.We performed an observational retrospective study to analyze the relationship between SNPs in the SLCO1B1 gene and the development of AEs in pediatric patients treated with MTX for JIA.Thirty patients with JIA were included, 22 females (73.3%), with a median age of 11 years (IQR 8.3–15). The most frequent JIA subtype was rheumatoid factor-positive polyarthritis (36.7%). Twenty patients (66.7%) reported AEs. The *1B haplotype was the most frequent in this group (53.3%) and conferred a higher risk of developing AEs (OR = 3.89, 95% CI = 1.23 -12.29, p = 0.03).Patients with the allele *1B may benefit from lower doses of MTX. SLCO1B1 genotyping is a promising technique to identify patients at higher risk of AEs during treatment with MTX, thus requiring dose optimization.Key Points• The most frequent SLCO1B1 haplotype in our population was *1B, also associated with a higher risk of developing adverse events (OR=3.89, 95% CI=1.23 -12.29, p=0.03). • SLCO1B1 genotyping is a promising tool to help identify patients at higher risk of MTX-related AEs.Results: The most frequent adverse events (AEs) of methotrexate (MTX) are gastrointestinal symptoms and hepatotoxicity, which can affect its adherence, leading to reduced effectiveness. The SLCO1B1 gene codes for a liver protein (OATP1B1) responsible for drug transportation. Genetic variations within the SLCO1B1 gene locus impact drug transport, leading to altered pharmacokinetic profiles, delayed MTX clearance, and increased risk of toxicity. This study aimed to determine the association between single nucleotide polymorphisms (SNPs) in the SLCO1B1 gene (rs4149056, rs2306283) with the development of AEs in patients with juvenile idiopathic arthritis (JIA) treated with MTX.We performed an observational retrospective study to analyze the relationship between SNPs in the SLCO1B1 gene and the development of AEs in pediatric patients treated with MTX for JIA.Thirty patients with JIA were included, 22 females (73.3%), with a median age of 11 years (IQR 8.3–15). The most frequent JIA subtype was rheumatoid factor-positive polyarthritis (36.7%). Twenty patients (66.7%) reported AEs. The *1B haplotype was the most frequent in this group (53.3%) and conferred a higher risk of developing AEs (OR = 3.89, 95% CI = 1.23 -12.29, p = 0.03).Patients with the allele *1B may benefit from lower doses of MTX. SLCO1B1 genotyping is a promising technique to identify patients at higher risk of AEs during treatment with MTX, thus requiring dose optimization.Key Points• The most frequent SLCO1B1 haplotype in our population was *1B, also associated with a higher risk of developing adverse events (OR=3.89, 95% CI=1.23 -12.29, p=0.03). • SLCO1B1 genotyping is a promising tool to help identify patients at higher risk of MTX-related AEs.Conclusions: The most frequent adverse events (AEs) of methotrexate (MTX) are gastrointestinal symptoms and hepatotoxicity, which can affect its adherence, leading to reduced effectiveness. The SLCO1B1 gene codes for a liver protein (OATP1B1) responsible for drug transportation. Genetic variations within the SLCO1B1 gene locus impact drug transport, leading to altered pharmacokinetic profiles, delayed MTX clearance, and increased risk of toxicity. This study aimed to determine the association between single nucleotide polymorphisms (SNPs) in the SLCO1B1 gene (rs4149056, rs2306283) with the development of AEs in patients with juvenile idiopathic arthritis (JIA) treated with MTX.We performed an observational retrospective study to analyze the relationship between SNPs in the SLCO1B1 gene and the development of AEs in pediatric patients treated with MTX for JIA.Thirty patients with JIA were included, 22 females (73.3%), with a median age of 11 years (IQR 8.3–15). The most frequent JIA subtype was rheumatoid factor-positive polyarthritis (36.7%). Twenty patients (66.7%) reported AEs. The *1B haplotype was the most frequent in this group (53.3%) and conferred a higher risk of developing AEs (OR = 3.89, 95% CI = 1.23 -12.29, p = 0.03).Patients with the allele *1B may benefit from lower doses of MTX. SLCO1B1 genotyping is a promising technique to identify patients at higher risk of AEs during treatment with MTX, thus requiring dose optimization.Key Points• The most frequent SLCO1B1 haplotype in our population was *1B, also associated with a higher risk of developing adverse events (OR=3.89, 95% CI=1.23 -12.29, p=0.03). • SLCO1B1 genotyping is a promising tool to help identify patients at higher risk of MTX-related AEs.The most frequent adverse events (AEs) of methotrexate (MTX) are gastrointestinal symptoms and hepatotoxicity, which can affect its adherence, leading to reduced effectiveness. The SLCO1B1 gene codes for a liver protein (OATP1B1) responsible for drug transportation. Genetic variations within the SLCO1B1 gene locus impact drug transport, leading to altered pharmacokinetic profiles, delayed MTX clearance, and increased risk of toxicity. This study aimed to determine the association between single nucleotide polymorphisms (SNPs) in the SLCO1B1 gene (rs4149056, rs2306283) with the development of AEs in patients with juvenile idiopathic arthritis (JIA) treated with MTX.We performed an observational retrospective study to analyze the relationship between SNPs in the SLCO1B1 gene and the development of AEs in pediatric patients treated with MTX for JIA.Thirty patients with JIA were included, 22 females (73.3%), with a median age of 11 years (IQR 8.3–15). The most frequent JIA subtype was rheumatoid factor-positive polyarthritis (36.7%). Twenty patients (66.7%) reported AEs. The *1B haplotype was the most frequent in this group (53.3%) and conferred a higher risk of developing AEs (OR = 3.89, 95% CI = 1.23 -12.29, p = 0.03).Patients with the allele *1B may benefit from lower doses of MTX. SLCO1B1 genotyping is a promising technique to identify patients at higher risk of AEs during treatment with MTX, thus requiring dose optimization.Key Points• The most frequent SLCO1B1 haplotype in our population was *1B, also associated with a higher risk of developing adverse events (OR=3.89, 95% CI=1.23 -12.29, p=0.03). • SLCO1B1 genotyping is a promising tool to help identify patients at higher risk of MTX-related AEs. [ABSTRACT FROM AUTHOR]

Uveitis is a major cause of visual impairment. Most uveitis cases have autoimmune etiology. Pediatric autoimmune uveitis may be associated with systemic diseases such as juvenile idiopathic arthritis or may arise as an isolated disorder. It may be accompanied by retinal vasculitis due to retinal microcirculation involvement. Nailfold capillaroscopy, a digital microscope, is a non-invasive tool for systemic microcirculation evaluation. We aimed to evaluate systemic microcirculation abnormalities in pediatric autoimmune uveitis. Twenty-five patients with pediatric autoimmune uveitis and 21 healthy children underwent detailed capillaroscopic evaluation. We assessed capillary density/mm, capillary morphology, capillary dimensions, and the presence or absence of microhemorrhages and avascular areas. The mean age of the study and control groups was 11.24 ± 3.03 and 9.9 ± 4.17 years, respectively. Most included patients had isolated uveitis and juvenile idiopathic arthritis (64% and 24%, respectively). The predominant uveitis subtype in the study was anterior uveitis (48%). A significant difference was found between cases and controls regarding mean capillary density (p-value = 0.0003) and the number of subjects having capillary density less than 7 (p-value = 0.002). Other capillaroscopic abnormalities did not show any significant difference between the studied groups. Mean capillary density did not correlate significantly with age, disease duration, or acute phase reactants. Children with autoimmune uveitis, whether isolated or as a part of systemic disease, may have systemic microcirculation involvement.Key Points• Idiopathic autoimmune uveitis is not always an isolated intraocular condition.• Systemic microcirculation involvement may occur in pediatric autoimmune uveitis, even in cases with isolated uveitis.• Nailfold capillaroscopy showed that capillary density in children with autoimmune uveitis is significantly reduced compared to healthy controls.Key Points• Idiopathic autoimmune uveitis is not always an isolated intraocular condition.• Systemic microcirculation involvement may occur in pediatric autoimmune uveitis, even in cases with isolated uveitis.• Nailfold capillaroscopy showed that capillary density in children with autoimmune uveitis is significantly reduced compared to healthy controls. [ABSTRACT FROM AUTHOR]

Objectives: To assess short- and long-term outcomes of ERA in a large monocentric cohort in Singapore. Methods: Children diagnosed with ERA according to ILAR criteria from 2002 to 2021 were recruited. Nonparametric statistics were used to describe the data. Outcomes were defined according to modified Wallace criteria, and probabilities and predictors were determined using Kaplan–Meier survival and logistic regression analyses. Results: One hundred fifty-one ERA patients (male 86%; Chinese 81%) were included. The median age at onset was 11.9 years (IQR: 9.4–13.9), and disease duration was 5.3 years (IQR: 2.9–8.4). At diagnosis, 39% of the patients had sacroiliitis. HLA-B27 was positive in 83%, and biologics were used in 72% of the patients. Clinical inactive disease (CID) was achieved in 92% of the patients, of which 27% achieved within 6 months. Sacroiliitis at diagnosis is an unfavorable predictor of early CID at 6 months. Medication was discontinued in one-third of the patients. Favorable predictor of medication withdrawal includes male gender, while unfavorable predictors include positive HLA-B27 and ANA. Two-thirds of the patients with CID had at least one disease flare. Sacroiliitis at diagnosis is a protective predictor of flare after stopping medication. Conclusion: Despite a high proportion of ERA patients achieving CID, only one-third could stop medication with high rates of disease flare. Unfavorable predictors include older age at onset, HLA-B27, and ANA positivity. While sacroiliitis at diagnosis is a negative predictor of CID at 6 months, it is associated with less disease flare after discontinuing medication. Key Points • Majority of the ERA patients achieved clinical inactive disease with treatment. • Only one-third of the patients could discontinue all medications with high rates of disease flare after. • Favorable outcome predictors include male gender and sacroiliitis at diagnosis, while unfavorable predictors include positive HLA-B27 and ANA. [ABSTRACT FROM AUTHOR]

The objective of this study was to determine the effectiveness of MRP8/14 as a predictor of disease flare in patients with juvenile idiopathic arthritis (JIA) following the withdrawal of methotrexate (MTX) in a routine clinical setting. All MRP8/14 tests performed at a single centre in a 27-month period were considered for analysis. Patients were assessed against criteria for inactive disease and subsequent disease flare. Decisions on whether or not to stop treatment were recorded. MRP8/14 results were assessed in conjunction with clinical information. Clinicians were also surveyed to investigate if MRP8/14 influenced their decision to discontinue MTX where this was available at that time point. One hundred four cases met the inclusion criteria during the study period. Although there was no significant difference in flares between patients with an elevated or low MRP8/14 value, in those who stopped MTX (n = 22), no patients with a low MRP8/14 (≤ 4000 ng/ml) result flared (follow-up time 12 months). Clinicians reported that for patients with clinically inactive disease and an elevated MRP8/14 result (> 4000 ng/ml), none would advise withdrawal of MTX. Low MRP8/14 was interpreted favourably when considering stopping MTX treatment in patients with JIA. Implementation of MRP8/14 testing has changed clinical practice at this centre. However, the observation that some patients in our cohort who had an elevated MRP8/14 value did not flare after stopping MTX for non-disease-related reasons highlights the need for further biomarkers to predict the risk of flare off medication in JIA and aid clinicians in treatment decisions. Key Points • First study of serum MRP8/14 measurement in clinical practice to inform treatment decisions in patients with JIA. • No patients with a low MRP8/14 test result went on to suffer a disease flare in 12 months of follow follow-up. • Further biomarkers are needed to predict the risk of flare off medication in JIA and treatment decisions. [ABSTRACT FROM AUTHOR]

Synovial osteochondromatosis is an extremely rare benign condition in children and adolescents that have joint pain as a presenting manifestation. It is usually monoarticular with the knee as the most common affected joint. In this article, we describe the case of a female adolescent suffering from debilitating chronic right knee pain initially mimicking juvenile idiopathic arthritis, who was subsequently diagnosed with primary synovial osteochondromatosis. We present a review of synovial osteochondromatosis focusing on the clinical manifestations, radiographic features, histopathologic findings, and treatment, with a summarized review of pediatric patients with initial musculoskeletal presentations who were ultimately diagnosed as synovial osteochondromatosis. Although synovial osteochondromatosis is rare in children and adolescents, this condition should be included in the differential diagnosis of joint pain and may mimic juvenile idiopathic arthritis. Appropriate diagnostic radiography, including both plain radiography and magnetic resonance imaging, is necessary to accurately diagnose this condition. We also emphasize the importance of a multidisciplinary team approach to managing patients with synovial osteochondromatosis. [ABSTRACT FROM AUTHOR]

This study aimed to compare the sensitivity and specificity of the European League Against Rheumatism/American College of Rheumatology-2019 (EULAR/ACR-2019) classification criteria with prior classification schemes for patients with childhood-onset systemic lupus erythematosus (cSLE). This single-center retrospective study examined 53 patients with cSLE and 53 patients having antinuclear antibody (ANA) titers ≥ 1:80 but not cSLE as controls. Sensitivity and specificity were calculated for the EULAR/ACR-2019 criteria, original criteria reported earlier in 2019, the ACR-1997 criteria, and the Systemic Lupus International Collaborating Clinics-2012 (SLICC-2012) criteria. The frequency of positivity in the cSLE group for each item of the EULAR/ACR-2019, ACR-1997, and SLICC-2012 criteria was determined. Characteristics of the misclassified patients were also investigated. All patients with cSLE had ANA titers ≥ 1:80. The non-SLE diagnoses included juvenile idiopathic inflammatory myopathies, primary Sjögren's syndrome (pSS), juvenile idiopathic arthritis, systemic sclerosis, mixed connective tissue disease (MCTD), and others. Sensitivities of the EULAR/ACR-2019 criteria, the original criteria, the ACR-1997 criteria, and the SLICC-2012 criteria were 100%, 100%, 86.8%, and 100%, respectively; the specificities were 84.9%, 92.5%, 98.1%, and 88.7%, respectively. In the cSLE group, the items of the SLE-specific antibody (100%), complement (98.1%), hematological (94.3%), and renal (84.9%) domains were frequently observed in the EULAR/ACR-2019 criteria. The EULAR/ACR-2019 criteria misclassified patient controls more frequently, especially those with MCTD or pSS, as having SLE than the previous criteria. The EULAR/ACR-2019 criteria for cSLE had high sensitivity but low specificity; the weighted scoring of the original criteria reported earlier in 2019 may confer higher specificity and be more appropriate for the classification of SLE in a pediatric population. Key Points • The EULAR/ACR-2019 criteria for cSLE had high sensitivity but low specificity. • The EULAR/ACR-2019 criteria more frequently misclassified non-SLE patients who did not have SLE, especially those with MCTD or pSS, as having SLE than the previous criteria in patients with childhood onset. • The weighted scoring of the original criteria reported earlier in 2019 may confer higher specificity and be a more appropriate classification of SLE for a pediatric population. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 infections in children are frequently asymptomatic or mild and can go unnoticed. This study aimed to describe the seroprevalence and clinical course of SARS-CoV-2 in a cohort of children with rheumatic diseases in a real-life setting and assess possible risk factors. A cross-sectional study was performed in a paediatric rheumatology unit (September 2020 to February 2021). At inclusion, a specific questionnaire was completed and SARS-CoV-2 serology was performed. Demographics, treatment and disease activity of patients with and without laboratory-confirmed SARS-CoV-2 infection were compared. A total of 105 children were included. SARS-CoV-2 infection was demonstrated in 27 patients (25.7%). The mean age was 11.8 years, and most patients were females (72.4%). The most frequent underlying condition was juvenile idiopathic arthritis (70.3%; 19/27). Patients received immunosuppressive treatment in 78% of cases (21/27). Overall, 44.4% (12/27) of infected patients were asymptomatic. A total of 66.7% (18/27) of patients did not require medical assistance. Three patients required hospital admission because of COVID-19. Children with confirmed SARS-CoV-2 infection were less frequently in remission (52% vs 72%; p 0.014). Moderate disease activity and treatment with oral corticosteroids were associated with higher risk for SARS-CoV-2 (OR 5.05; CI 95%: 1.56–16.3 and OR 4.2; CI 95%: 1.26–13.9, respectively). In a cohort of Spanish paediatric patients with rheumatic diseases, clinical course of COVID-19 was mild, with more than one third of asymptomatic cases. Higher disease activity and oral corticosteroids appear to be risk factors for SARS-CoV-2 infection. Key Points • We aimed to investigate the seroprevalence of SARS-CoV-2 infection in a cohort of Spanish paediatric patients with RD, testing both symptomatic and asymptomatic patients. We also compared treatment and disease activity of patients with and without laboratory-confirmed SARS-CoV-2 infection. • In our cohort of 105 paediatric patients with rheumatic diseases, the clinical course of COVID-19 was mild and 44% of cases were asymptomatic. Three cases required hospital admission with no complications. Seroprevalence was 20%. • No association was found between disease activity or treatment with corticosteroids and symptomatic or asymptomatic infection. Higher disease activity and treatment with oral corticosteroids appeared to be risk factors for laboratory-confirmed SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Introduction: Bone marrow edema (BME) is one of the main imaging characteristics of juvenile idiopathic arthritis (JIA) in children and rheumatoid arthritis (RA) in adult. Previous studies have shown that BME occurred in approximately 64% of adults with RA and was a key predictor of poor prognosis. But BME with JIA has not been of great concern. Therefore, we evaluated the prevalence, characteristics, and prognosis of knee joint BME in children with JIA. Methods: In this retrospective study, we included children with JIA and knee joint involvement from January 2017 to December 2019. BME was evaluated according to the Juvenile Arthritis MRI Scoring system. Clinical characteristics were compared between the BME group and the non-BME group. The characteristics and prognosis of the BME were observed. Results: A total of 128 children with 136 knee joint MRI data were identified, with 37 knee joints (27.2%) having BME. BME has positive correlation with synovial hypertrophy (Rs = 0.562, p = 0.019). There were significant differences in age (p = 0.010) and disease duration (p = 0.013) between the BME and non-BME groups. BME was found to be more common in older children and the patients with long duration of disease. Locations with BME were the lateral tibial plateau (17/37, 45.9%), the lateral weight-bearing femur (16/37, 43.2%), the medial tibial plateau and the medial femoral condyle (both with 15/37, 40.5%), and the medial weight-bearing femur (12/37, 32.4%). The lateral femoral condyle and both the lateral and medial sides of the patella were rarely involved. Of the 15 BME joints with the MRI follow-up data (interval 6.5 ± 3.0 months), the lesions disappeared or improved within 12 months after the treatments in 13 (86.7%) joints. Conclusions: The prevalence of knee BME in JIA was 27.2%. There was positive correlation between BME and synovial hypertrophy. Older children and children with long disease duration had a higher risk for BME, which was commonly a late presentation and more likely involved the weight-bearing surfaces of the joint. The overall prognosis was satisfactory after the standard treatments. Key Points • To the best of our knowledge, this paper is the first one to investigate the MRI manifestation in JIA focus on knee BME sign. [ABSTRACT FROM AUTHOR]

Introduction: Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease that can present with various forms of arthritis. This retrospective study aims to evaluate the characteristics of patients with arthritis in a large pediatric cohort of FMF patients. Methods: The demographic and clinical data were extracted from electronic medical records. Patients with arthritis were grouped as arthritis of FMF and arthritis of FMF-associated diseases. Results: A total of 541 patients were followed with a diagnosis of FMF in the last 5 years. Acute arthritis of FMF (n: 138) was the most common cause. It showed a recurrent course in the majority with a longer duration than other attack symptoms. Significantly higher frequencies of biallelic exon 10 and M694V mutations, erysipelas-like erythema, and protracted febrile myalgia were detected in these patients, particularly in those older than 2 years of age. Sacroiliitis of FMF was the second most common cause (n: 19). Patients with acute arthritis and sacroiliitis of FMF needed higher doses of colchicine. One patient with neonatal-onset FMF and M694V homozygosity was diagnosed with protracted arthritis. Arthritides of FMF-associated diseases including IgA vasculitis (n: 10), juvenile idiopathic arthritis (n: 9), chronic nonbacterial osteomyelitis (n: 5), and inflammatory bowel disease (n: 2) were detected in 26 patients. Conclusions: Arthritis is an important clinical finding of FMF mostly associated with M694V mutations. The frequency of protracted arthritis is declined, whereas sacroiliitis of FMF and arthritis of associated diseases expand the spectrum of arthritis. This study represents the changing face and current perspectives of arthritis in FMF. Key Points • Arthritis is an important clinical finding of familial Mediterranean fever (FMF) that can present in various forms • Arthritis is most likely associated with M694V mutations • The frequency of protracted arthritis is declined whereas sacroiliitis of FMF and arthritis of associated diseases expand the spectrum of arthritis in FMF [ABSTRACT FROM AUTHOR]

Objective: We aimed to find out the asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence among pediatric patients with rheumatic diseases and healthy children and to compare them with each other. Methods: Patients with familial Mediterranean fever (FMF), juvenile idiopathic arthritis (JIA), and juvenile systemic lupus erythematosus (jSLE) and healthy children as healthy control (HC) group who remained asymptomatic during the pandemic are examined by ELISA immunoglobulin (Ig) A and IgG tests in this cross-sectional study. Results: Overall, 149 subjects (90 females) were included in the study. While IgA was positive in 15 subjects (10%) (HC: 8, jSLE: 3, FMF: 2, JIA: 2; p = 0.196), IgG was positive in 14 subjects (9.4%) (HC: 7, JIA: 5, FMF: 1, jSLE: 1; p = 0.156). Nineteen subjects (12.75%) were IgA or IgG positive (HC: 8, JIA: 5, jSLE: 3, FMF: 3; p = 0.644). Although not significant, seropositivity was more often in HC group. Both IgA and IgG positivity were not found to be related to age, sex, underlying rheumatic diseases, and received treatments of the patients. Conclusion: We revealed that patients with childhood-onset rheumatic diseases, even if they receive immunosuppressive medication such as biologic or conventional disease-modifying anti-rheumatic drugs, might have an asymptomatic SARS-CoV-2 infection, similarly to their healthy peers. Key points • Although it has been already known that children are most likely to have asymptomatic SARS-CoV-2 infection, there is a lack of data on the disease course of children with rheumatic disease. • There was no significant difference regarding the asymptomatic SARS-CoV-2 seropositivity rates between healthy children and the patients with childhood-onset rheumatic diseases. • Patients with childhood-onset rheumatic diseases, even if they receive immunosuppressive medication, might have asymptomatic SARS-CoV-2 infection, similarly to their healthy peers. [ABSTRACT FROM AUTHOR]

Objectives: Most patients with progressive pseudorheumatoid dysplasia (PPRD) are initially misdiagnosed because of disease rarity and lack of awareness by most clinicians. The purpose of this study was to provide further early diagnostic options and potential treatment to patients with PPRD. Methods: A retrospective study was performed by collecting and organizing clinical manifestations, radiographic features, laboratory test results, genetic test outcome, treatment, and follow-up records of the patients with PPRD. Age of diagnosis and genotype-phenotype correlation were further analyzed. Results: Nine PPRD children with causative CCN6 mutation were included. There were 3 pairs of siblings and 1 patient from inbred family. Five patients were primarily misdiagnosed as juvenile idiopathic arthritis (JIA). The interval between onset of symptoms and definite diagnosis of 8 patients varied from 3.6 to 20 years. Symptoms at the onset included enlarged and stiff interphalangeal joints of the fingers, gait disturbance, or joint pain. Laboratory tests revealed normal range of inflammatory parameters. Radiographic findings disclosed different degrees of abnormal vertebral bodies and epiphyseal enlargement of the interphalangeal joints. After the treatment of calcitriol in 5 patients with low level 25-hydroxyvitamin D3 for around 1.25 years to 1.75 years, 2 patients kept stable, while 3 of them improved gradually. Conclusions: Combining the patient's family history, clinical features, normal inflammatory markers, and the characteristic radiographic findings, the clinical diagnosis of PPRD for the patients could be obtained at very early stage of the disease. The patients with PPRD carrying c.624dupA variant in CCN6 may have delayed onset. Underlying vitamin D deficiency should be sought and corrected in patients with PPRD. Key Points • Children with progressive pseudorheumatoid dysplasia (PPRD) are easily misdiagnosed with juvenile idiopathic arthritis (JIA). • PPRD is different from JIA with normal range of inflammatory parameters and abnormal vertebral bodies. • Underlying vitamin D deficiency should be sought and corrected in patients with PPRD. [ABSTRACT FROM AUTHOR]

Autologous hematopoietic stem cell transplantation (HSCT) has been recognized as treatment alternative for patients with severe, refractory autoimmune rheumatic diseases (ARDs). Usually, anti-thymocyte globulin (ATG)-containing conditioning regimens are employed; however, ATG is unavailable in some developing nations. We report our 15-year clinical experience autografting patients with ARDs with an ATG-free conditioning regimen and a brief assessment of patient-reported outcomes post-HSCT. All patients had active disease and were resistant to multiple lines of treatment. Event-free survival (EFS) was assessed using the Kaplan-Meier method. Eight patients underwent autologous HSCT. Diagnoses included juvenile idiopathic arthritis (n = 3), systemic lupus erythematosus (n = 2), systemic sclerosis (n = 2), and rheumatoid arthritis (n = 1). Median time from diagnosis to HSCT was 3 years (0.75–19). Hematological recovery was documented in all recipients, and 4 patients (50%) completed the procedure in a completely ambulatory setting. Five (62.5%) patients achieved complete response and 3 (37.5%) partial response. The median EFS was 7 months (95% CI, 4.97–9.02), and the 1-year EFS rate was 21.9% (95% CI, 18.25–25.76). Transplant-related mortality was 0%, and 1 recipient died 8 years post-HSCT due to chronic kidney disease. Six (75%) patients presented steroid dosage reduction post-HSCT, and 2 (25%) perceived improvement in functionality despite having relapsed. HSCT is a viable treatment alternative for selected patients with severe therapy-resistant ARDs, as an improvement in disease management and quality of life was documented. The need remains to elucidate the characteristics of the optimal HSCT candidate, as well as the adequate conditioning regimen when ATG is not available. Key Points • Despite advances in the treatment of autoimmune rheumatic diseases, some patients remain refractory. In this context, autologous hematopoietic stem cell transplantation (HSCT) rises as a viable alternative. • Of 8 HSCT recipients with autoimmune rheumatic diseases, 5 (62.5%) patients achieved complete response and 3 (37.5%) partial response, with a 1-year event-free survival of 21.9%. • Transplant-related mortality was 0%, with 4 (50%) patients autografted in a completely outpatient setting. • Even when relapse presented, patients reported an improvement in functionality and quality of life; also, a better response to DMARDs and a reduction in steroid dependency post-HSCT were documented. [ABSTRACT FROM AUTHOR]

Background: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic condition of childhood. Genetic association studies have revealed several JIA susceptibility loci with the strongest effect size observed in the human leukocyte antigen (HLA) region. Genome-wide association studies have augmented the number of JIA-associated loci, particularly for non-HLA genes. The aim of this study was to identify new associations at non-HLA loci predisposing to the risk of JIA development in Estonian patients. Methods: We performed genome-wide association analyses in an entire JIA case–control sample (All-JIA) and in a case–control sample for oligoarticular JIA, the most prevalent JIA subtype. The entire cohort was genotyped using the Illumina HumanOmniExpress BeadChip arrays. After imputation, 16,583,468 variants were analyzed in 263 cases and 6956 controls. Results: We demonstrated nominal evidence of association for 12 novel non-HLA loci not previously implicated in JIA predisposition. We replicated known JIA associations in CLEC16A and VCTN1 regions in the oligoarticular JIA sample. The strongest associations in the All-JIA analysis were identified at PRKG1 (P = 2,54 × 10−6), LTBP1 (P = 9,45 × 10−6), and ELMO1 (P = 1,05 × 10−5). In the oligoarticular JIA analysis, the strongest associations were identified at NFIA (P = 5,05 × 10−6), LTBP1 (P = 9,95 × 10−6), MX1 (P = 1,65 × 10−5), and CD200R1 (P = 2,59 × 10−5). Conclusion: This study increases the number of known JIA risk loci and provides additional evidence for the existence of overlapping genetic risk loci between JIA and other autoimmune diseases, particularly rheumatoid arthritis. The reported loci are involved in molecular pathways of immunological relevance and likely represent genomic regions that confer susceptibility to JIA in Estonian patients. Key Points • Juvenile idiopathic arthritis (JIA) is the most common childhood rheumatic disease with heterogeneous presentation and genetic predisposition. • Present genome-wide association study for Estonian JIA patients is first of its kind in Northern and Northeastern Europe. • The results of the present study increase the knowledge about JIA risk loci replicating some previously described associations, so adding weight to their relevance and describing novel loci. • The study provides additional evidence for the existence of overlapping genetic risk loci between JIA and other autoimmune diseases, particularly rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study is to evaluate a possible negative action of lockdown, during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, in the follow-up of juvenile idiopathic arthritis (JIA) patients. Methods: We compared the number of JIA reactivations in the period March–July 2020 to the same months of 2018 and 2019. Results: A total of 10 JIA reactivations have been documented on 58 patients (17%) visited in the period March–July 2018; 10 reactivations on 61 patients (16%) in the period March–July 2019; and 19 reactivations on 39 patients (49%) in the period March–July 2020, with a statistically significant increase (p <0.001). The other 19 patients who should have been visited during the same period, contacted by phone, indicated remission. Therefore, we hypothesize that the effective number of reactivations in the period March–July 2020 would be 19/58 patients (33%) which remains significantly greater than in the previous 2 years (p < 0.05). Among the 19 JIA patients reactivated in 2020, 3 spontaneously stopped the basic treatment due to parents' choice for fear of serious complications in case of SARS-CoV-2 infection and 4 had poor compliance with underlying treatment. In addition, 14/19 reactivated JIA patients did not perform the scheduled check according to the follow-up. In fact, the mean time interval between two follow-up visits was significantly greater in 2020 (157 ± 53 days, p < 0.0001) vs 2018 (108 ± 68 days) and 2019 (107 ± 40 days). Conclusions: We have found a significant increase in JIA reactivations in the period March–July 2020 compared to the same interval of 2018 and 2019. This increase may have been caused by poor compliance with background treatment, as documented in 7/19 JIA patients reactivated, and by a greater interval in follow-up checks. Therefore, it is necessary, in occasion of a new pandemic and lockdown, to implement greater controls using more appropriate telemedicine tools. Key Points • COVID-19 pandemic lockdown had a negative effect on the follow-up of JIA patients. • A significant increase in JIA reactivations was found during the lockdown. • Poor therapeutic compliance and follow-up checks have been proven during the lockdown. • It is necessary to improve telemedicine tools and scientific information during a pandemic and lockdown. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the study was to assess the sexual and mental health of women suffering from connective tissue diseases and to determine the potential interrelationships between the studied clinical variables and sexual and mental health. Methods: The study was conducted in a group of women with connective tissue diseases. To assess somatic health, we used The Health Assessment Questionnaire (HAQ-DI), and to assess sexual health, we used the Female Sexual Function Index (FSFI) and Sexual Satisfaction Questionnaire (KSS). The mental health was assessed by using the Hospital Anxiety and Depression Scale (HADS-M) and the PERMA-Profiler (PL). Results: The study involved 81 women suffering from connective tissue diseases, especially rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), ankylosing spondylitis (AS) and juvenile idiopathic arthritis (JIA). Clinical symptoms of sexual dysfunction were observed in 54% women. The biggest difficulties occur in sexual desire, orgasm and arousal. Patients had symptoms of anxiety and depressive disorders. Higher levels of anxiety and depression are associated with poorer overall sexual functioning and better overall sexual functioning, and all its dimensions are associated with a higher level of mental well-being. There was also an observed relationship with the functional limitation due to pain and duration of the disease. Conclusion: The study confirms the existence of difficulties in the sexual functioning of women suffering from connective tissue diseases and shows the relationship between sexual and mental health and basic disease. The observed relationships are important information in the treatment and medical care of people with this group of rheumatic diseases. Key Points • The article presents one of the few studies about sexual functioning of Polish population women with connective tissue diseases. • The aim was to assess the sexual and mental health of women with various connective tissue diseases and determine the potential interrelationships between the clinical variables and sexual and mental health. • The study confirms difficulties in the sexual functioning of women with connective tissue diseases. The biggest difficulties occur in sexual desire, orgasm and arousal. Patients also had mental disorders symptoms. • The study presents conclusions and indications which may be important and help specialists approach the treatment process in an interdisciplinary way. [ABSTRACT FROM AUTHOR]

The co-existence of juvenile idiopathic arthritis (JIA)/rheumatoid arthritis (RA) and focal segmental glomerulosclerosis (FSGS) is rare, and the existence of co-pathogenesis remains unknown. In this study, we analyzed the clinical and gene mutation characteristics of a patient with JIA and FSGS caused by a NPHS2 gene mutation, and evaluated the potential connections between these two diseases. We summarized the clinical manifestations, related examination results, and gene mutation characteristics of the patient who presented at our center and six reported cases of arthritis with renal disease. Most of the cases were polyarticular arthritis with varying degrees of renal damage (hematuria, proteinuria, and renal dysfunction) and different prognoses. Among these patients, two developed end-stage renal disease (ESRD), with one dying as a result, while the other patients had a relatively good prognosis. Patients with a family history of renal disease had a poor prognosis. After excluding occasional factors and drug influences, our analysis indicated the existence of co-pathogenesis of arthritis with renal damage (especially FSGS). NPHS2 mutations might account for the family aggregation. Therefore, evaluation of more clinical cases is necessary to further clarify the underlying co-pathogenesis of these diseases. [ABSTRACT FROM AUTHOR]

Objective: To assess short- and long-term outcomes and predictors of juvenile idiopathic arthritis (JIA) children treated with contemporary therapy and compare those with reports elsewhere. Methods: Children with JIA were recruited from our web-based REgistry for Childhood Onset Rheumatic Diseases (RECORD) from 1997 to 2015. Disease status was defined using modified Wallace criteria. Nonparametric statistics described the data. Kaplan-Meier survival and logistic regression analyses were used to estimate probabilities and to determine predictors of outcomes. Results: A total of 251 children with JIA (62% males, 71% Chinese) were included. Median follow-up duration was 2.9 years (range 0.1–17.5). Short-term clinical inactive disease (CID) was attained in 37% with 62% systemic JIA (sJIA) and 47% persistent oligoarthritis (oJIA). Methotrexate (OR 0.34) decreased but sJIA (OR 3.25) increased chance of attaining CID at 6 months. Overall, 79% of patients achieved CID within 2 years (sJIA 92%, the highest, and RF+ polyarthritis 50%, the lowest probability). Biologics were associated with CID attainment (OR 2.73). One-half of patients flare after CID, median 1.2 years (IQR 0.71–1.97). Late CID achievement predicted flare (OR 2.15). Only 15% had clinical remission off medication (none RF+ polyarthritis and 7% ERA). Only 13% of patients had active arthritis as young adults and 22% had active arthritis at last visit. Conclusion: Despite high proportion of JIA patients attaining CID, only one-fourth could stop all medications for at least 1 year. Persistent oJIA patients were less likely to achieve clinical remission on medication and ERA patients had the least chance stopping medications. One-tenth of patients had active arthritis as young adults. Key Points • Majority of Asian children with JIA attained inactive disease within 2 years after diagnosis. • Outcome predictors were different from reports from the West. • Despite high inactive disease numbers, only one-in-four JIA patients discontinued treatment within 5 years. [ABSTRACT FROM AUTHOR]

Objective: The sternoclavicular joint (SCJ), an important link between the appendicular and axial skeleton, though involved in 41% of rheumatoid arthritis patients, has not been studied in juvenile idiopathic arthritis (JIA). Hence, this cross-sectional study was done to delineate the magnetic resonance imaging (MRI) findings in SCJ in JIA and compare with the clinical examination to diagnose SCJ arthritis. Methods: Of the 116 JIA patients attending the pediatric rheumatology clinic, twenty-one patients (42 SC joints) were evaluated by 1.5 T MRI using the four components of early and late inflammatory changes—synovial hypertrophy, bone marrow edema (BME), cartilage lesions, and bone erosions. Results were compared with clinical assessment of SCJ arthritis. Results: Of the 42 SCJ evaluated (21/116 patients), MRI changes were seen in 27 SCJs (15 patients, 12.9% of 116 JIA patients). Early MRI changes were seen in 60% of joints found normal on clinical examination, with as much as 1/4th of them revealing late destructive changes. Synovial hypertrophy, BME, cartilage lesions, and bone erosions were seen in 5, 15, 4, and 10 patients, respectively. Sensitivity and specificity of clinical examinations to evaluate SC joint involvement were 55.5% and 53.3%, respectively. Conclusion: MRI evaluation of the SCJ in JIA revealed findings in 15/21 enrolled patients. BME, bone erosions, synovial hypertrophy, and cartilage lesions were seen in 15, 10, 5, and 4 enrolled patients, respectively. Clinical examination was found to be neither sensitive nor specific. Key Points • MRI could delineate both early and late inflammatory changes in SCJ in JIA. BME, bone erosions, synovial hypertrophy, and cartilage lesions were seen in 15, 10, 5, and 4 enrolled patients, respectively. • The frequency of SC joint involvement in JIA was at least 12.9% of patients in our study. • Clinical examination for evaluating SC joint arthritis has low sensitivity (55.5%) and specificity (53.3%). [ABSTRACT FROM AUTHOR]

Background: To compare outcomes of a short and long weaning strategy of anti-tumor necrosis factor (aTNF) in our prospective juvenile idiopathic arthritis (JIA) cohort.JIA patients on subcutaneous adalimumab with at least 6 months of follow-up were recruited (May 2010–Jan 2022). Once clinical remission on medication (CRM) was achieved, adalimumab was weaned according to two protocols—short (every 4-weekly for 6 months and stopped) and long (extending dosing interval by 2 weeks for three cycles until 12-weekly intervals and thereafter stopped) protocols. Outcomes assessed were flare rates, time to flare, and predictors.Of 110 JIA patients, 77 (83% male, 78% Chinese; 82% enthesitis-related arthritis) underwent aTNF weaning with 53% on short and 47% on long weaning protocol. The total flare rate during and after stopping aTNF was not different between the two groups. The time to flare after stopping aTNF was not different (p = 0.639). Positive anti-nuclear antibody increased flare risk during weaning in long weaning group (OR 7.0, 95%CI: 1.2–40.8). Positive HLA-B27 (OR 6.5, 95%CI: 1.1–30.4) increased flare risks after stopping aTNF.Duration of weaning aTNF may not minimize flare rate or delay time to flare after stopping treatment in JIA patients. Recapture rates for inactive disease at 6 months remained high for patients who flared after weaning or discontinuing medication.Key Points• It may not be necessary to taper aTNF over a long period in JIA patients as the duration of spacing out aTNF therapy after achieving CRM may not minimize the flare rate or delay time to flare.• A positive HLA-B27 increased the flare risks after aTNF discontinuation, regardless of the weaning duration.• Recapture rates for CID at 6 months remained high for patients who flared after weaning or discontinuing medication.Research design and methods: To compare outcomes of a short and long weaning strategy of anti-tumor necrosis factor (aTNF) in our prospective juvenile idiopathic arthritis (JIA) cohort.JIA patients on subcutaneous adalimumab with at least 6 months of follow-up were recruited (May 2010–Jan 2022). Once clinical remission on medication (CRM) was achieved, adalimumab was weaned according to two protocols—short (every 4-weekly for 6 months and stopped) and long (extending dosing interval by 2 weeks for three cycles until 12-weekly intervals and thereafter stopped) protocols. Outcomes assessed were flare rates, time to flare, and predictors.Of 110 JIA patients, 77 (83% male, 78% Chinese; 82% enthesitis-related arthritis) underwent aTNF weaning with 53% on short and 47% on long weaning protocol. The total flare rate during and after stopping aTNF was not different between the two groups. The time to flare after stopping aTNF was not different (p = 0.639). Positive anti-nuclear antibody increased flare risk during weaning in long weaning group (OR 7.0, 95%CI: 1.2–40.8). Positive HLA-B27 (OR 6.5, 95%CI: 1.1–30.4) increased flare risks after stopping aTNF.Duration of weaning aTNF may not minimize flare rate or delay time to flare after stopping treatment in JIA patients. Recapture rates for inactive disease at 6 months remained high for patients who flared after weaning or discontinuing medication.Key Points• It may not be necessary to taper aTNF over a long period in JIA patients as the duration of spacing out aTNF therapy after achieving CRM may not minimize the flare rate or delay time to flare.• A positive HLA-B27 increased the flare risks after aTNF discontinuation, regardless of the weaning duration.• Recapture rates for CID at 6 months remained high for patients who flared after weaning or discontinuing medication.Results: To compare outcomes of a short and long weaning strategy of anti-tumor necrosis factor (aTNF) in our prospective juvenile idiopathic arthritis (JIA) cohort.JIA patients on subcutaneous adalimumab with at least 6 months of follow-up were recruited (May 2010–Jan 2022). Once clinical remission on medication (CRM) was achieved, adalimumab was weaned according to two protocols—short (every 4-weekly for 6 months and stopped) and long (extending dosing interval by 2 weeks for three cycles until 12-weekly intervals and thereafter stopped) protocols. Outcomes assessed were flare rates, time to flare, and predictors.Of 110 JIA patients, 77 (83% male, 78% Chinese; 82% enthesitis-related arthritis) underwent aTNF weaning with 53% on short and 47% on long weaning protocol. The total flare rate during and after stopping aTNF was not different between the two groups. The time to flare after stopping aTNF was not different (p = 0.639). Positive anti-nuclear antibody increased flare risk during weaning in long weaning group (OR 7.0, 95%CI: 1.2–40.8). Positive HLA-B27 (OR 6.5, 95%CI: 1.1–30.4) increased flare risks after stopping aTNF.Duration of weaning aTNF may not minimize flare rate or delay time to flare after stopping treatment in JIA patients. Recapture rates for inactive disease at 6 months remained high for patients who flared after weaning or discontinuing medication.Key Points• It may not be necessary to taper aTNF over a long period in JIA patients as the duration of spacing out aTNF therapy after achieving CRM may not minimize the flare rate or delay time to flare.• A positive HLA-B27 increased the flare risks after aTNF discontinuation, regardless of the weaning duration.• Recapture rates for CID at 6 months remained high for patients who flared after weaning or discontinuing medication.Conclusion: To compare outcomes of a short and long weaning strategy of anti-tumor necrosis factor (aTNF) in our prospective juvenile idiopathic arthritis (JIA) cohort.JIA patients on subcutaneous adalimumab with at least 6 months of follow-up were recruited (May 2010–Jan 2022). Once clinical remission on medication (CRM) was achieved, adalimumab was weaned according to two protocols—short (every 4-weekly for 6 months and stopped) and long (extending dosing interval by 2 weeks for three cycles until 12-weekly intervals and thereafter stopped) protocols. Outcomes assessed were flare rates, time to flare, and predictors.Of 110 JIA patients, 77 (83% male, 78% Chinese; 82% enthesitis-related arthritis) underwent aTNF weaning with 53% on short and 47% on long weaning protocol. The total flare rate during and after stopping aTNF was not different between the two groups. The time to flare after stopping aTNF was not different (p = 0.639). Positive anti-nuclear antibody increased flare risk during weaning in long weaning group (OR 7.0, 95%CI: 1.2–40.8). Positive HLA-B27 (OR 6.5, 95%CI: 1.1–30.4) increased flare risks after stopping aTNF.Duration of weaning aTNF may not minimize flare rate or delay time to flare after stopping treatment in JIA patients. Recapture rates for inactive disease at 6 months remained high for patients who flared after weaning or discontinuing medication.Key Points• It may not be necessary to taper aTNF over a long period in JIA patients as the duration of spacing out aTNF therapy after achieving CRM may not minimize the flare rate or delay time to flare.• A positive HLA-B27 increased the flare risks after aTNF discontinuation, regardless of the weaning duration.• Recapture rates for CID at 6 months remained high for patients who flared after weaning or discontinuing medication.To compare outcomes of a short and long weaning strategy of anti-tumor necrosis factor (aTNF) in our prospective juvenile idiopathic arthritis (JIA) cohort.JIA patients on subcutaneous adalimumab with at least 6 months of follow-up were recruited (May 2010–Jan 2022). Once clinical remission on medication (CRM) was achieved, adalimumab was weaned according to two protocols—short (every 4-weekly for 6 months and stopped) and long (extending dosing interval by 2 weeks for three cycles until 12-weekly intervals and thereafter stopped) protocols. Outcomes assessed were flare rates, time to flare, and predictors.Of 110 JIA patients, 77 (83% male, 78% Chinese; 82% enthesitis-related arthritis) underwent aTNF weaning with 53% on short and 47% on long weaning protocol. The total flare rate during and after stopping aTNF was not different between the two groups. The time to flare after stopping aTNF was not different (p = 0.639). Positive anti-nuclear antibody increased flare risk during weaning in long weaning group (OR 7.0, 95%CI: 1.2–40.8). Positive HLA-B27 (OR 6.5, 95%CI: 1.1–30.4) increased flare risks after stopping aTNF.Duration of weaning aTNF may not minimize flare rate or delay time to flare after stopping treatment in JIA patients. Recapture rates for inactive disease at 6 months remained high for patients who flared after weaning or discontinuing medication.Key Points• It may not be necessary to taper aTNF over a long period in JIA patients as the duration of spacing out aTNF therapy after achieving CRM may not minimize the flare rate or delay time to flare.• A positive HLA-B27 increased the flare risks after aTNF discontinuation, regardless of the weaning duration.• Recapture rates for CID at 6 months remained high for patients who flared after weaning or discontinuing medication. [ABSTRACT FROM AUTHOR]

There is no single diagnostic test for any rheumatic disease. The diagnosis of a rheumatic disease is made by the sum of the findings in history, physical examination, laboratory, and imaging tests. A differential diagnosis list in pediatric rheumatology is quite long and mainly includes malignant, infectious, and inherited metabolic disorders. We aim to present cases that were referred to a pediatric rheumatology outpatient clinic with provisional diagnosis of a rheumatic disease but finally diagnosed with a non-rheumatic disease in order to emphasize the importance of differential diagnoses. Eight cases were presented in this manuscript. Five cases were referred with the provisional diagnosis of juvenile idiopathic arthritis. Sarcoidosis, chronic non-bacterial osteomyelitis, and autoinflammatory disease were the provisional referral diagnoses in three patients. Definitive diagnoses of the patients were as follows: acute lymphoblastic leukemia (two cases), bilineage acute leukemia, Hodgkin lymphoma, brucellosis, mucolipidosis type III, anhidrotic ectodermal dysplasia, and Freiberg disease. In children presenting with rheumatic complaints malignant, infectious and inherited metabolic disorders should always be in the differential diagnosis list of a pediatric rheumatologist. Alternative diagnoses should always be considered even in patients with a rheumatic disease when the patient does not respond to treatment or follows an unusual clinical course. Key Points • Diagnosis of a rheumatic disease is made by exclusion of all other pathologies. • Malignant and infectious diseases may mimic the signs and symptoms of a rheumatic disease. [ABSTRACT FROM AUTHOR]

To study disease activity during pregnancy and obstetric outcomes in patients with juvenile idiopathic arthritis (JIA) upon different subsets and with focus on medication use. Retrospective observational study of 22 pregnancies in 16 JIA patients (95.5% Caucasian) who were followed between 2010 and 2018. Disease activity, flares and medications were recorded before conception, during each trimester and postpartum period. Pregnancies occurred in 10 (45.5%) oligoarticular extended (OLA-E), 6 (27.3%) in polyarticular (PLA), 4 in (18.2%) systemic (SYS), 1 (4.5%) in oligoarticular persistent (OLA-P) and 1 (4.5%) in enthesitis-related arthritis (ERA) JIA patients. The median age at disease diagnosis and at conception was 5.5 and 28 years (respectively). The median disease duration was 20 years. Nineteen (95%) pregnancies started in a period of stable disease remission. Among the 22 pregnancies, 20 ended with a live birth (90.9%). No spontaneous miscarriages occurred; two voluntary interruption of pregnancy were performed. There were 7 flares in 6/20 pregnancies (35%) and 8 flares (8/22, 36.4%) occurred in postpartum period, all of them in OLA-E and PLA patients. Seven patients (35%) were taking biological disease-modifying anti-rheumatic drugs (bDMARDs) at conception, and 6 of them stopped this treatment at positive pregnancy test. Five patients resumed bDMARDs either during pregnancy (3 exposed during the third trimester) or puerperium due to a flare. Four preterm deliveries (20%) were recorded, all in patients who had a flare during pregnancy. The preconception counselling should include the evaluation of disease subset, as OLA-E and PLA may flare more than other subsets, especially if bDMARDs are discontinued at positive pregnancy test. Continuation of bDMARDs during pregnancy should be considered to minimize the risk of adverse pregnancy outcomes, particularly preterm delivery. Key Points • In our cohort, all the flares during pregnancy and 75% of postpartum flares were observed in patients who withdrew bDMARDs and cDMARDs at the beginning of pregnancy. • Flares were observed only in PLA and OLA-E patients. • Preterm delivery occurred in 20% of the pregnancies; all of these patients had a disease flare during pregnancy. [ABSTRACT FROM AUTHOR]

Background: Juvenile idiopathic arthritis (JIA) is the most prevalent rheumatic disease in children. The core stability exercises ensure proper muscular strength and balance around the lumbo-pelvic-hip complex. Objective: This study evaluated whether the use of core stability exercises would increase the effectiveness of conventional physical therapy (PT) in enhancing bone mineralization and improving functional capacity in children with polyarticular JIA. Methods: Thirty-three children with polyarticular JIA (age; 10–14 years) assigned randomly into two groups: the control group (n = 16) received the conventional PT, and the study group (n = 17) received the core stability exercises in addition to the same conventional PT program. Both core stability and conventional PT exercises continued for 3 months. The measures of bone mineralization and functional ability were investigated by dual-energy X-ray absorptiometry (DXA) device and 6-min walk test (6MWT), respectively, at baseline and immediately post-treatment. Results: Analysis of covariance (ANCOVA) revealed significant differences between groups in favor of the study group regarding measures of bone mineralization of lumbar spine and femoral neck regions as P < 0.05, except for volumetric bone mineral density of lumbar spine the P > 0.05. There was a significant difference between the two groups concerning functional capacity measured in 6MWT (P < 0.05), where children in the study group walked 531.71 ± 90.59 m compared with the control group 509.31 ± 73.10 m. Conclusion: Core stability exercises are an effective adjunctive therapy to enhance bone health status and improve functional capacity in children with polyarticular JIA. Key Points • In addition to conventional physical therapy, core stability exercises had a definite effect on improving bone health status and quality of life in children with polyarticular juvenile idiopathic arthritis. • Improved bone mineralization and functional capacity due to core stability exercises contain two parts: strengthening training and controlling equilibrium. [ABSTRACT FROM AUTHOR]

Objective: SB5 showed comparable efficacy and safety profile in respect to adalimumab originator (ADA) in randomized clinical trials of rheumatoid arthritis (RA) and psoriasis. We aimed to describe the efficacy and safety of SB5 after switching from ADA in RA, axial spondyloarthritis (axSpA), psoriatic arthritis (PsA) and juvenile idiopathic arthritis (JIA) patients. Method: Adult RA, PsA, axSpA, JIA patients treated with ADA for at least 6 months, switched to SB5 in stable clinical conditions, were eligible. Data on safety, activity indexes and patient-reported outcomes were collected at baseline, 3 and 6 months after switching. Results: Eighty-two patients (19 RA, 28 PsA, 32 axSpA and 3 JIA; 45 females, mean age 54 ± 14 years, disease duration 13 ± 7 years, ADA duration 6 ± 3 years) were enrolled. RA patients showed stable conditions, while PsA patients showed an increase in both HAQ, DAS28(CRP) and DAPSA and axSpA patients an increase in VAS pain, VAS patient disease activity and ASDAS, both at 3 months. There were changes in the concomitant medications profile, with regression of activity indexes increases at 6 months. Adverse events were reported by 33.7% patients at 3 months and 16.6% patients at 6 months, mostly disease flares and infectious events. Two patients stopped SB5. Conclusions: Despite temporary changes in the concomitant medication profile for mild disease flares, our real-life data replicate the safety profile of switching from ADA to SB5 in RA, with additional data for its applicability in PsA and axSpA patients, further supporting switching to biosimilars in treating inflammatory rheumatic conditions. Key Points • Switching from adalimumab originator to SB5 is feasible in real life rheumatic inflammatory joint diseases. • Mild disease flares can present after switching from originator adalimumab to SB5, in particular in axial spondyloarthritis and psoriatic arthritis. • Changes in concomitant medications profile allows the control of minor disease flares presenting after switching from adalimumab originator to SB5. [ABSTRACT FROM AUTHOR]

Objectives: To examine the clinical characteristics, treatment and outcomes of juvenile idiopathic arthritis (JIA) patients evaluated in Singapore and compare those with reports elsewhere. Methods: Patients with JIA were recruited from our Singapore pediatric rheumatology registry from January 1997 to December 2015. Demographic, clinical, treatment, and outcome data were retrospectively collected. Nonparametric statistics were used to describe the data. Chi-squared, Mann-Whitney U, or Kruskal-Wallis tests were applied to compare differences between groups where appropriate. Multivariate logistic regression analyses were used to identify predictors for clinical parameters. Results: Two hundred eighty-seven JIA patients with 60.6% males of predominantly Chinese descent were included in the study. The median onset age was 9 years (IQR 5.3–12.6), and the median follow-up duration was 30.1 months (IQR 9.1–61.7). Enthesitis-related arthritis (ERA, 32.8%) followed by persistent oligoarthritis (31.0%) was the most common. Elbow or ankle involvement predicted oligoarthritis extension (OR 15.8 (95% CI: 2.3–108.3, p = 0.005), 8.1 (95% CI: 1.5–45.3, p = 0.017)). JIA-associated uveitis was rare (2.8%) which paralleled the less common positive-ANA rate. Majority of our ERA patients had HLA-B27 (79.8%), together with older age predicted sacroiliitis (OR 4.7 (95% CI: 2.0–11.1, p < 0.05), OR 1.2 (95% CI: 1.1–1.3, p = 0.002)). TMJ involvement was under-reported. Methotrexate remained the most common DMARD used, but 36% of patients required biologics for which ERA and polyarthritis were the majority. Joint damage was rare. Conclusion: This study highlights geographical and ethnic differences in JIA epidemiology. Compared with reports elsewhere, our JIA population had many unique findings and good functional outcomes requiring regional study validation. Key points • ERA is the most prominent JIA subtype in Singapore with high prevalence of HLA-B27. • JIA-associated uveitis is rare in SEA and is not associated with ANA or JIA-subtypes. • Elbow and/or ankle involvement at presentation is associated with oligoarthritis extension in our JIA cohort. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate and compare the clinical implications of common inflammatory markers in systemic rheumatic diseases (SRDs). Method: We investigated the profiles of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and white blood cell (WBC) count in treatment-naïve patients with SRDs, osteoarthritis and pneumonia diagnosed at Seoul National University Hospital during 2004–2016. SRDs included rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), ankylosing spondylitis (AS), systemic sclerosis (SSc), idiopathic inflammatory myopathy (IIM) and adult-onset Still's disease (AOSD). Associations between inflammatory markers were evaluated using Pearson's correlation and regression analysis. ROC curve analysis was performed to examine the predictive value of inflammatory markers for SRD diagnosis. Results: We identified a total of 1191 patients. Leukocytosis was present in < 20% SRD patients. There was marked variability in ESR and CRP levels among different SRDs. The highest mean CRP levels (mean ± SD, mg/dL) were observed in AOSD (11.3 ± 7.9), followed by RA (2.0 ± 3.3), IIM (1.8 ± 3.5), SLE (1.5 ± 3.1), SSc (0.6 ± 1.3) and AS (0.08 ± 0.1). Mean ESR (mm/h) was also highest in AOSD (71.2 ± 31.0), followed by SLE (47.3 ± 34.2), RA (45.5 ± 30.6), IIM (40.8 ± 24.8) and SSc (27.8 ± 26.0). All SRDs showed significant positive correlations between ESR and CRP: greatest in RA (r = 0.53, p < 0.001) and weakest in SLE (r = 0.20, p = 0.03). WBC correlated weakly with CRP but not with ESR in most SRDs. While the AUC for WBC count was less than that of ESR or CRP, the AUC for ESR and CRP were similar in SRD. The optimal cuff-off values for inflammatory markers predicting SRD were within or slightly above the normal limit. Conclusions: ESR, CRP and WBC are not always elevated in treatment-naïve patients with SRD. Individual SRDs have a unique profile of inflammatory markers. However, routine inflammatory markers should still be interpreted with caution when diagnosing and assessing disease activity in those with SRD. Key Points •Leukocytosis and elevation of ESR and CRP are not always present in all systemic rheumatic diseases. •Inflammatory markers are often dissociated and they are not specific for disease diagnosis. •Better biomarkers, which measure disease-specific local and systemic inflammation, are needed. [ABSTRACT FROM AUTHOR]