Early Juvenile Idiopathic Arthritis Research Articles

Pre-Rheumatology Referral Consultation and Investigation Pattern in Children with Joint Complaints: Focus on Juvenile Idiopathic Arthritis.

The diagnosis of juvenile idiopathic arthritis (JIA) is often entrusted to the pediatric rheumatologist specialist. Timely referral to a specialized center is crucial. This study aims to assess the consultation and investigation patterns of patients with joint complaints before rheumatology referral. This longitudinal cohort study included patients with joint complaints who were referred to the Pediatric Rheumatology Unit. The cohort included 301 patients (58% female), 50 of them (17%) diagnosed with JIA. Compared to patients with orthopedic conditions or functional diseases, JIA patients had seen more specialists (p < 0.01) and received a quicker diagnosis (p < 0.01). Patients with early JIA diagnosis (within 3 months from symptoms onset) were younger (8.46 vs. 11.5 years old; p = 0.04), more frequently female (78% vs. 47%, p = 0.03), and with higher erythrocyte sedimentation rate (ESR) values (37 vs. 9 mm/h; p = 0.02) than those diagnosed later. Patients with a late diagnosis of JIA had a significantly longer median time between the first healthcare visit and the PR referral (25 vs. 101 days; p < 0.01). The main contributor to diagnostic delay in JIA was the time required for PR referral after the first healthcare consult. Younger age, female sex, and higher ESR values were associated with earlier diagnosis of JIA.

Towards stratified treatment of JIA: machine learning identifies subtypes in response to methotrexate from four UK cohorts

Methotrexate (MTX) is the gold-standard first-line disease-modifying anti-rheumatic drug for juvenile idiopathic arthritis (JIA), despite only being either effective or tolerated in half of children and young people (CYP). To facilitate stratified treatment of early JIA, novel methods in machine learning were used to i) identify clusters with distinct disease patterns following MTX initiation; ii) predict cluster membership; and iii) compare clusters to existing treatment response measures. Discovery and verification cohorts included CYP who first initiated MTX before January 2018 in one of four UK multicentre prospective cohorts of JIA within the CLUSTER consortium. JADAS components (active joint count, physician (PGA) and parental (PGE) global assessments, ESR) were recorded at MTX start and over the following year. Clusters of MTX 'response' were uncovered using multivariate group-based trajectory modelling separately in discovery and verification cohorts. Clusters were compared descriptively to ACR Pedi 30/90 scores, and multivariate logistic regression models predicted cluster-group assignment. The discovery cohorts included 657 CYP and verification cohorts 1241 CYP. Six clusters were identified: Fast improvers (11%), Slow Improvers (16%), Improve-Relapse (7%), Persistent Disease (44%), Persistent PGA (8%) and Persistent PGE (13%), the latter two characterised by improvement in all features except one. Factors associated with clusters included ethnicity, ILAR category, age, PGE, and ESR scores at MTX start, with predictive model area under the curve values of 0.65-0.71. Singular ACR Pedi 30/90 scores at 6 and 12 months could not capture speeds of improvement, relapsing courses or diverging disease patterns. Six distinct patterns following initiation of MTX have been identified using methods in artificial intelligence. These clusters demonstrate the limitations in traditional yes/no treatment response assessment (e.g., ACRPedi30) and can form the basis of a stratified medicine programme in early JIA. Medical Research Council, Versus Arthritis, Great Ormond Street Hospital Children's Charity, Olivia's Vision, and the National Institute for Health Research.

Application of the new classification proposal for juvenile idiopathic arthritis of the pediatric rheumatology international trials organization in a group of Mexican patients.

Apply the PRINTO classification proposal for diagnosing Juvenile Idiopathic Arthritis (JIA) to Mexican patients, analyzing demographic, clinical, and laboratory characteristics. Cross-sectional study analyzing patients diagnosed with JIA using International League of Associations for Rheumatology (ILAR 2001) criteria over two years at a national rheumatic disease center. Reclassification was done using the Pediatric Rheumatology International Trials Organization (PRINTO) proposal. Comparisons were made between antinuclear antibodies (ANAs) positive vs. negative and rheumatoid factor (RF) positive vs. negative patients. Seventy-six patients were analyzed, mostly female. Median age was lower in systemic JIA (sJIA) and early onset JIA with positive ANAs (eoANA JIA). ANAs was present in 78.6% of patients. Reclassification according to PRINTO disorders showed RF positive polyarticular JIA, sJIA, and enthesitis-related JIA (ER JIA) reclassified to RF JIA, sJIA, and enthesitis/spondylitis-related JIA (ESR JIA) by 100%, 94.7%, and 80%, respectively. The ILAR category with the most variation was RF negative polyarticular JIA. Early disease onset was associated with a lower probability of positive RF after adjusting for sex, age, and ANAs. No association was found between ANAs positive vs. negative in adjusted multivariate analysis. We found compatibility of sJIA, RF positive polyarticular JIA, and RE JIA categories with sJIA, RF JIA, and ESR JIA disorders, respectively. Differences were noted in variables such as sex and the number of affected joints. There was high ANAs positivity; however, few patients were classified into eoANA JIA disorder, with only one presenting uveitis. Most patients were classified as other JIA.

Antibiotic exposure in prenatal and early life and risk of juvenile idiopathic arthritis: a nationwide register-based cohort study

ObjectivesEarly antibiotic exposure influences the gut microbiota which is believed to be involved in the pathogenesis of juvenile idiopathic arthritis (JIA). We aimed to investigate the association between systemic antibiotics...

Normal neonatal TREC and KREC levels in early onset juvenile idiopathic arthritis

Dysregulated central tolerance predisposes to autoimmune diseases. Reduced thymic output as well as compromised central B cell tolerance checkpoints have been proposed in the pathogenesis of juvenile idiopathic arthritis (JIA). The aim of this study was to investigate neonatal levels of T-cell receptor excision circles (TRECs) and kappa-deleting element excision circles (KRECs), as markers of T- and B-cell output at birth, in patients with early onset JIA. TRECs and KRECs were quantitated by multiplex qPCR from dried blood spots (DBS), collected 2-5days after birth, in 156 children with early onset JIA and in 312 matched controls. When analysed from neonatal dried blood spots, the median TREC level was 78 (IQR 55-113) in JIA cases and 88 (IQR 57-117) copies/well in controls. The median KREC level was 51 (IQR 35-69) and 53 (IQR 35-74) copies/well, in JIA cases and controls, respectively. Stratification by sex and age at disease onset did not reveal any difference in the levels of TRECs and KRECs. T- and B-cell output at birth, as measured by TREC and KREC levels in neonatal dried blood spots, does not differ in children with early onset JIA compared to controls.

19 Maternal and early childhood exposures in relation to juvenile idiopathic arthritis

Abstract Background Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children. JIA likely has a complex aetiology, with multiple genetic and environmental factors contributing to its development. Existing data on associations between maternal and early childhood exposures and JIA is rare. Previous studies showed potential role for prematurity, number of siblings and infections. Objectives The aim of our study is to assess maternal and early childhood exposures in patients with JIA. Methods Mothers of children with JIA followed in rheumatology department were asked about maternity related data as well as the course of perinatal period of the child with JIA based on the International League of Associations for Rheumatology (ILAR) criteria. Exposure information from birth included: Maternal factors (age when they had the first child, age when they had the child with JIA, plurality (singleton, twin/multiple gestation), number of prior fetal losses, number of prior births; delivery method (vaginal, cesarean section)) and also information about birth weight (low (&amp;lt;2500 grams), normal (2500– 4000 grams), excessive (4000+ grams)); size for- gestational-age and gestational age (preterm, normal term, post term) and postpartum complications. Results Thirty children (sixteen females and fourteen males) with JIA were included. The most common type of JIA was enthesitis-related in 13 cases, then oligoarthritis in 8 cases, polyarthritis without rheumatoid factor in 4 cases, polyarthritis with positive rheumatoid factor in 2 cases and psoriatic arthritis in 3 cases. The mean age of the mothers was 27.1 years [22–40] when they had their first child and 30.27 years [22–42] when they had their child with JIA. They were nulliparous in 40% of the cases. All of the children were from a singleton pregnancy. Thirty percent of the mothers had at least one prior fetal loss before they had their child with JIA. During their pregnancy with their child with JIA, five mothers had pre-eclampsia and two of them had gestational diabetes. None of them smoked during the pregnancy. Only 2 children had preterm birth. Birth weight was normal (2.500–4.000 grams) in 24 cases, low in 3 cases (&amp;lt;2.500 grams) and above normal (&amp;gt;4000 grams) in 3 cases. Size for gestational age was normal in all cases. Nineteen mothers had vaginal delivery and eleven had cesarean section. Neonatal complications were noted in 7 cases who needed to be admitted to neonatal intensive care unit (1 for hypoglycemia, 1 for jaundice, 2 for infection, 1 for respiratory distress and two because of preterm birth). Maternal complications were noted in four cases: 2 postpartum hemorrhage and 2 postpartum infections. Conclusion Our study assessed maternal and early childhood exposures in patients with JIA. Further studies are required to explore associations between these factors and the occurrence of the disease for a better knowledge of etiologies of JIA and for a possible prevention from this pathology.

Clinical remission and subsequent relapse in patients with juvenile idiopathic arthritis: predictive factors according to therapeutic approach

BackgroundJuvenile idiopathic arthritis constitutes a significant cause of disability and quality of life impairment in pediatric and adult patients. The aim of this study was to ascertain clinical remission (CR) and subsequent relapse in juvenile idiopathic arthritis (JIA) patients, according to therapeutic approach and JIA subtype. Evidence in literature regarding its predictors is scarce.MethodsWe conducted an observational, ambispective study. Patients diagnosed of JIA, treated with synthetic and/or biologic disease modifying antirheumatic drugs (DMARD) were included and followed-up to December 31st, 2015. Primary outcome was clinical remission defined by Wallace criteria, both on and off medication. In order to ascertain CR according to therapeutic approach, DMARD treatments were divided in four groups: 1) synthetic DMARD (sDMARD) alone, 2) sDMARD combined with another sDMARD, 3) sDMARD combined with biologic DMARD (bDMARD), and 4) bDMARD alone.ResultsA total of 206 patients who received DMARD treatment were included. At the time the follow-up was completed, 70% of the patients in the cohort had attained CR at least once (144 out of 206), and 29% were in clinical remission off medication (59 out of 206).According to treatment group, CR was more frequently observed in patients treated with synthetic DMARD alone (53%). Within this group, CR was associated with female sex, oligoarticular persistent subtypes, ANA positivity, Methotrexate treatment and absence of HLA B27, comorbidities and DMARD toxicity. 124 DMARD treatments (62%) were withdrawn, 64% of which relapsed. Lower relapse rates were observed in those patients with persistent oligoarticular JIA (93%) when DMARD dose was tapered before withdrawal (77%).ConclusionsMore than two thirds of JIA patients attained CR along the 9 years of follow-up, and nearly one third achieved CR off medication. Females with early JIA onset, lower active joint count and ANA positivity were the ones achieving and sustaining remission more frequently, especially when receiving synthetic DMARD alone and in the absence of HLA B27, comorbidities or previous DMARD toxicity.

Nothing about us without us: involving patient collaborators for machine learning applications in rheumatology

Novel machine learning methods open the door to advances in rheumatology through application to complex, high-dimensional data, otherwise difficult to analyse. Results from such efforts could provide better classification of...

Juvenile Idiopathic Arthritis-Associated Chronic Uveitis: Recent Therapeutic Approaches.

Pediatric patients with early onset (before the age of 6 years), antinuclear antibody positive, oligoarticular or polyarticular juvenile idiopathic arthritis (JIA), and some children with no arthritis may develop chronic, anterior uveitis. Recent recommendations insist on the need to perform slit lamp examination every 3 months for at least 5 years in early onset JIA patients in order to diagnose uveitis before complications develop. Local steroid therapy is usually the first-line treatment. However, in patients requiring steroid eye drops for several months, systemic immunomodulatory therapy is indicated. Methotrexate (MTX) is then prescribed in most cases; however, some patients also need anti-tumor necrosis factor alpha monoclonal antibody therapy and, in some cases, other biologics to control uveitis and avoid long-term ocular damage. Expert ophthalmologists and pediatricians must be involved in taking care of such patients. Immunomodulatory treatment must not be too easily interrupted and may even be intensified in some cases, particularly if there is a need for optimal disease control before ophthalmologic surgery. In good responders to MTX and/or biologics, treatment must be maintained at least 1 year, possibly even 2 years after achieving remission before tapering treatment intensity.

Role of MRI &amp; US in the Evaluation of Knee Joint Affection in Patients with Juvenile Idiopathic Arthritis

Abstract Background: Juvenile Idiopathic Arthritis (JIA) is defined as arthritis of unknown etiology beginning before the age of 16 years and persisting for at least 6 weeks, while excluding other known conditions. Aim of Study: The purpose of this study is to highlight the beneficial role of MRI & US in the evaluation of knee joint affection in patients with juvenile idiopathic arthritis, especially in early cases. Patients and Methods: The study was carried out on fourty patients (26 females and 14 males), referred to the Radiology Department of Kasr El-Ainy Hospital from Abo El-Rish Pediatric Hospital. Their age ranged from 2.5 years up to 13 years. All patients underwent examination of the more symp-tomatic knee joint using MRI with intravenous contrast (Gadolinium) and Ultrasound (US) examinations. The results of the ultrasound were compared to those of MRI, with the MRI being the gold standard of diagnosis. Results: Among the studied cases ultrasound was able to detect joint effusion in all cases as a compressible anechoic area. It was able to detect synovitis as synovial thickening and increased vascularity on power Doppler in all cases which is evident mainly in the suprapatellar recess. The accuracy of US regarding both effusion and synovitis was 100%. Ultra-sound had great potential to identify the normal cartilage and allows for differentiation of the abnormal morphology such as loss of clarity, irregularity, and defects on the surface. In our study ultrasound was able to demonstrate most of the cases. The overall accuracy regarding cartilage changes was 90%. In this study six of the cases had bone erosions which were detected on MRI. US was able to detect four of these cases. The overall accuracy of US regarding erosions was 95%. Conclusion: Ultrasound has the ability to demonstrate knee joint pathology in early JIA which can help start early treatment or modify already existing one to prevent permanent joint damage. At this point in time, however, it is not possible to determine that ultrasound is superior to MRI, especially regarding bone erosions and the fact that it is operator depend-ent and needs experience.

Low Serum IGF-1 in Boys with Recent Onset of Juvenile Idiopathic Arthritis.

Background Liver-derived insulin-like growth factor-1 (IGF-1) contributes bone formation. Decreased IGF-1 levels are common in juvenile idiopathic arthritis (JIA), but whether IGF-1 is related to sex and differ during the pathogenic progress of JIA is unknown. Objective The aim of this study was to examine IGF-1 levels in boys and girls with newly diagnosed JIA, with established JIA and in controls. Methods The study group included 131 patients from the Estonian population-based prevalence JIA study. Blood samples were obtained from 27 boys and 38 girls with early JIA (≤1 month from the diagnosis), 29 boys and 36 girls with established JIA (mean disease duration 18 months), and from 47 age- and sex-matched controls. Results IGF-1 levels in boys were significantly decreased in early JIA compared to male controls, while IGF-1 levels in girls were comparable between JIA and controls. In early JIA, IGF-1 levels were 12-fold lower in boys relative to girls. In controls, IGF-1 levels correlated with both age and height, while these correlations were lost in boys with early JIA. Conclusion We report a sex-dependent deficiency in serum IGF-1 in boys with early JIA, which argues for sex-related differences in biological mechanisms involved in the disease pathogenesis.

Effect of Monotherapy with Methotrexate, Etanercept and their Combination on the Quality of Life in Children with Early and Late Juvenile Idiopathic Arthritis: A Prospective Study

Background. An important goal of treating patients with juvenile idiopathic arthritis (JIA) is to achieve the best quality of life associated with health. Objective. Our aim was to assess the impact of methotrexate plus etanercept therapy on the quality of life of patients with early and late JIA. Methods. The prospective study included patients with early and late JIA without systemic manifestations. The patients’ quality of life was assessed with the help of questionnaires for children and parents: the Pediatric Quality of Life Inventory (PedsQL) Generic Core Scale, the Pediatric Quality of Life Inventory (PedsQL) Rheumatology Module, and the Health Utilities Index Mark 3 (HUI3). The quality of life was assessed prior to the therapy and after one, six, and 12 months of treatment. Results. 150 children with JIA aged 5.1 (2.0; 17.7) years; 50 children aged 4.0 (2.3–11.4) years in the group of etanercept monotherapy, 50 children aged 5.0 (3.2–9.0) years in the group of methotrexate monotherapy, and 50 children aged 9.9 (6.4–13.0) years in the group of methotrexate plus etanercept combination therapy. All groups showed low scores on all questionnaires before treatment, compared to healthy children. In the course of therapy, there was a tendency for score increase to almost 1.0 according to the HUI3 questionnaire in all groups. After one year of etanercept therapy, the parameters of the quality of life of children with early JIA did not differ from healthy children; the score increased from 56 to 90 p = 0.942 according to the physical functioning scale and from 60 to 85 p = 0.889 according to the emotional functioning scale. In the 2nd group, there was a tendency for score increase, but a statistically significant difference was found across all scales of the questionnaire. After 12 months of etanercept plus methotrexate combination therapy in patients with late JIA, the questionnaire analysis showed that the responses of healthy children and children with JIA differed with probability p = 0.001 for the physical functioning scale, p = 0.001 for the social functioning scale, p = 0.001 for role functioning, and p = 0.001 for the total score. The score increase from 60 to 85 p = 0.789 was noted for emotional functioning scales. Conclusion. The use of questionnaires to assess the quality of life in children with severe chronic diseases can significantly improve the efficacy of treatment and ensure its control.

Growth patterns in early juvenile idiopathic arthritis: Results from the Childhood Arthritis Prospective Study (CAPS).

ObjectivesTo investigate early vertical growth patterns and factors associated with poor growth in a modern inception cohort of UK children with juvenile idiopathic arthritis (JIA) using data from the Childhood Arthritis Prospective Study (CAPS).MethodsA study period of 3 years was chosen. Children included in this analysis had a physician diagnosis of JIA and had height measurements available at both baseline and at 3-years of follow-up. Height is presented as z-scores calculated using World Health Organisation growth standards for age and gender. Growth over the 3-year period was assessed using change in z-score and height velocity. Univariable and multivariable linear regressions were used to identify factors associated with height z-score at baseline and change of height z-score at 3 years.Results568 patients were included; 65% female, median baseline age 7.4 years [interquartile range (IQR) 3.6, 11.2], median symptom duration at presentation 5.5 months [IQR 3.1, 11.6]. Height z-score decreased significantly from baseline to 3 years (p ≤ 0.0001); baseline median height z-score was −0.02 (IQR −0.71, 0.61), decreasing to −0.47 (IQR −1.12, 0.24) at 3 years. Growth restriction, defined as change of height z-score ≤−0.5, was observed in 39% of patients. At 3 years, higher baseline height z-score was the strongest predictor for a negative change in height z-score [−0.3 per unit of baseline height z-score (95% CI: −0.36, −0.24), p < 0.0001].ConclusionsAlthough overall height at 3 years after initial presentation to rheumatology is within the population norm, as a cohort, children with JIA experience a reduction of growth in height over the first 3 years of disease. Late presentation to paediatric rheumatology services is associated with lower height at presentation. However, patients with the lowest height z scores at presentation were also the most likely to see an improvement at 3 years. The impact of JIA on growth patterns is important to children and families and this study provides useful new data to support informed clinical care.

Research progress of Kawasaki disease and arthritis in children

Kawasaki disease(KD) or incomplete KD(IKD) is a systemic vasculitis predominantly affecting young children.Clinical manifestations include fever with no obvious origin, skin damage, abnormalities of mucous membrane and lymph nodes.The disease is often accompanied by serious cardiovascular complications such as coronary artery aneurysm, therefore it attracts more and more attention.But arthritis or arthralgia complicates over one-third of KD or IKD patients.So early-onset arthritis is often indistinguishable from early juvenile idiopathic arthritis, especially systemic-onset juvenile idiopathic arthritis(SoJIA). KD and SoJIA are considered to be different diagnoses for children with long-term fever, rash, swollen lymph nodes, and more importantly, the treatment procedures are very different, but it is difficult to completely distinguish the two diseases, especially the IKD and early SoJIA.So in this paper, we will summarize the relationship between KD and arthritis in children, which aims to remind clinicians to pay attention for the diagnosis of KD and IKD.We suggest that physicians should be alert of the fact that they must individualize every patient′s management, rather than merely care by the guidelines, which will delay the treatment. Key words: Kawasaki disease; Arthritis; Systemic-onset juvenile idiopathic arthritis; Children

Evaluation of Efficacy and Safety of Etanercept Therapy in Patients with Early and Late Juvenile Idiopathic Arthritis without Systemic Manifestations

Background: An issue related to the terms of assignment of genetically engineered biological agents to patients with juvenile idiopathic arthritis (JIA) still remains debatable in pediatric rheumatology. Objective: Our aim was to evaluate the efficacy and safety of etanercept therapy in early and late JIA without systemic manifestations. Methods: An observational comparative study. The participants were divided into 2 groups. Patients of the treatment group (n = 98) — with early arthritis (lasting less than 2 years), and patients of the control group (n = 99) — with late arthritis (lasting more than 2 years). All children received etanercept in a dose of 0.4 mg/kg body weight 2 times per week subcutaneously. The efficacy of the therapy was evaluated for 3 years using the criteria of the American College of Rheumatology (ACRрedi), remission criteria by C. Wallace and JADAS71 index. Results: Total number of patients with JIA under the study is 197. After 6 months, the improvement according to the ACRpedi criteria 30/50/70 was recorded in 97/97/91% and 98/96/88%, and after 1 year — in 100/100/99% and 99/94/92% of patients with early and late arthritis, respectively. The efficacy of etanercept according to criteria by C. Wallace and JADAS71 index in early arthritis was higher than in late arthritis within 2 years of observation. Conclusion : Etanercept is more effective in early JIA than in late JIA without systemic manifestations.

Experience of Parenteral Administration of Methotrexate in a Female Patient Suffering from Early Juvenile Idiopathic Arthritis and Uveitis

Represented here is a case of early juvenile idiopathic arthritis associated with uveitis diagnosed in a three-year-old female patient subject to treatment with the standard methotrexate dosage. At the initial stage of treatment, the child demonstrated severe articular syndrome, inflammatory reactions affecting eyeball surfaces, increased laboratory indicators of the illness and functional insufficiency. Successful overcoming of methotrexate resistance through dosage increased up to 20 mg/m 2 of body surface per week was described. Over three months of subcutaneous methotrexate treatment with a 15 mg/m 2 -per-week dose, the child showed milder joint exudation an, arthralgia, less lengthy morning stiffness, although there was no 50% improvement based on ACR pedi criteria, and uveitis was first recognized in the subactive phase. The dose was increased up to 20 mg/m 2 per week. By the eighth week of methotrexate treatment, uveal inflammation reversed. Non-active phase and remission were detected in 6 and 12 months respectively. The remission has persisted for 6 years. No side effects have been observed throughout methotrexate treatment.

Association of neopterin as a marker of immune system activation and juvenile rheumatoid arthritis activity

ObjectiveTo evaluate neopterin plasma concentrations in patients with active juvenile idiopathic arthritis (JIA) and correlate them with disease activity. MethodsSixty patients diagnosed as active JIA, as well as another 60 apparently healthy age‐ and gender‐matched children as controls, were recruited from the Pediatrics Allergy and Immunology Clinic, Ain Shams University. Disease activity was assessed by the Juvenile Arthritis Disease Activity Score 27 (JADAS‐27). Laboratory investigations were performed for all patients, including determination of hemoglobin concentration (Hgb), erythrocyte sedimentation rate (ESR), and C‐reactive protein. Serum concentrations of tumor necrosis factor‐alpha (TNF‐α), interleukin‐6 (IL‐6), monocyte chemoattractant protein‐1 (MCP‐1), and neopterin were measured. ResultsSignificant differences were found between JIA patients and controls with regard to the mean levels of Hgb, ESR, TNF‐α, IL‐6, and MCP‐1 (p<0.05). A statistically significant higher mean level serum neopterin concentration (p<0.05) was found in JIA patients (20.43±8.73 nmol/L) than in controls (6.88±2.87 nmol/L) (p<0.05). Positive significant correlations were detected between serum neopterin and ESR, TNF‐α, IL‐6, MCP‐1, and JADAS‐27 (p<0.05). No correlation was found between serum neopterin and CRP (p>0.05). Multiple linear regression analysis showed that JADAS‐ 27 and ESR were the main variables associated with serum neopterin in JIA patients (p<0.05). ConclusionThe elevation of plasma neopterin concentrations in early JIA patients may indicate stimulation of immune response. Serum neopterin can be used as a sensitive marker for assaying background inflammation and disease activity score in JIA patients.

Association of neopterin as a marker of immune system activation and juvenile rheumatoid arthritis activity

ObjectiveTo evaluate neopterin plasma concentrations in patients with active juvenile idiopathic arthritis (JIA) and correlate them with disease activity. MethodsSixty patients diagnosed as active JIA, as well as another 60 apparently healthy age- and gender-matched children as controls, were recruited from the Pediatrics Allergy and Immunology Clinic, Ain Shams University. Disease activity was assessed by the Juvenile Arthritis Disease Activity Score 27 (JADAS-27). Laboratory investigations were performed for all patients, including determination of hemoglobin concentration (Hgb), erythrocyte sedimentation rate (ESR), and C-reactive protein. Serum concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and neopterin were measured. ResultsSignificant differences were found between JIA patients and controls with regard to the mean levels of Hgb, ESR, TNF-α, IL-6, and MCP-1 (p<0.05). A statistically significant higher mean level serum neopterin concentration (p<0.05) was found in JIA patients (20.43±8.73 nmol/L) than in controls (6.88±2.87 nmol/L) (p<0.05). Positive significant correlations were detected between serum neopterin and ESR, TNF-α, IL-6, MCP-1, and JADAS-27 (p<0.05). No correlation was found between serum neopterin and CRP (p>0.05). Multiple linear regression analysis showed that JADAS- 27 and ESR were the main variables associated with serum neopterin in JIA patients (p<0.05). ConclusionThe elevation of plasma neopterin concentrations in early JIA patients may indicate stimulation of immune response. Serum neopterin can be used as a sensitive marker for assaying background inflammation and disease activity score in JIA patients.

Serum Angiogenesis Markers and Their Correlation with Ultrasound-Detected Synovitis in Juvenile Idiopathic Arthritis.

Synovial angiogenesis is considered to be an important early step in the pathogenesis of juvenile idiopathic arthritis (JIA). In this study we assessed levels of angiogenic markers in serum or synovial fluid and their possible relevance to disease activity or degree of ultrasound signs of synovial inflammation and angiogenesis in early JIA. The concentration of vascular endothelial growth factor (VEGF), its soluble receptors 1 and 2 (sVEGF-R1, sVEGF-R2), and angiopoietins 1 and 2 (ANG-1, ANG-2) were evaluated in 43 JIA patients and 23 healthy controls. Synovial angiogenesis was assessed by means of Power-Doppler Ultrasonography (PDUS), according to the fourth-grade vascularity scale. VEGF and its receptors' (sVEGF-R1, sVEGF-R2) serum levels were significantly higher in JIA patients (p = 0.002). We found large variation in serum ANG-1 and ANG-2 levels. The PDUS imaging identified increased synovial microvascular blood flow in 15 (35.7%) examined JIA children. Intensity of joint vascularization correlated with higher serum VEGF and its levels was lowest in grade 0 and highest in grade 3 (p < 0.007 and p < 0.001, resp.). In conclusion, the high correlation between synovial microvascular blood flow, serum angiogenic proteins, and symptoms of synovitis may indicate its important role in pathogenesis of JIA.

AB0216 Serum Angiogenesis Markers and their Association with Ultrasound-Detected Synovitis in the Evaluation of Disease Activity in Juvenile Idiopathic Arthritis

BackgroundSynovial angiogenesis, defined as a complex process of developing new blood vessels from the existing microvascular bed, is considered to be an important early step in the course and pathogenesis...