JIA Subtypes Research Articles

P14 The Irish National Centre for Paediatric Rheumatology experience of moving from IV to SC tocilizumab (TCZ)

Abstract Background Tocilizumab (TCZ) is a monoclonal antibody that targets the interleukin 6 receptor. It is approved for use in children over the age of 2 years with systemic onset juvenile idiopathic arthritis (SoJIA) and polyarticular juvenile idiopathic arthritis (pJIA) who have not responded to treatment with non-steroidal agents, corticosteroids and methotrexate mono-therapy. Previous studies from our centre have shown a positive response to IV TCZ with high rates of remission. TCZ has recently been licensed for administration via the SC route. The aim of this study is to determine how many patients receiving IV TCZ were successfully changed to SC TCZ in the first 6 months after SC TCZ paediatric licensing was obtained and to document any adverse events. Methods Retrospective review of patients with SoJIA or pJIA who were on IV TCZ and changed to S/C TCZ over a 6 month period from October 2018 to April 2019. Patients were identified from an in-house aseptic pharmacy database Clinichemo®. All patients on IV TCZ were identified and cross checked against the Hibernian patient referral system for home SC TCZ administration. Criteria for changing included fulfilling Wallace Criteria for clinical remission and appropriate JIA subtype. Results were analysed using Microsoft Excel. Results 28 patients receiving IV TCZ in October 2018 were identified. 8 were excluded due to either a diagnosis other than SoJIA/pJIA or changing to an alternative biologic. Of the 20 eligible patients, 10 had successfully changed by April 2019. Of those who did not change, 1 is due to change in May 2019, 2 did not wish to change, indicating personal preference as their reason. A total of 7 were deemed unsuitable for medication change due to ongoing active disease. Of the 10 patients who successfully changed, 2 had SoJIA and 8 had pJIA. All were commenced on a dose of 162mg with frequency varying from 1 to 4 weekly as per Summary of Product Characteristics. There was no significant change in ESR, CRP, LFT or WCC demonstrated pre or post change in administration route. No adverse events were reported. 1 patient subsequently changed back to IV administration due to patient preference. Conclusion Our experience to date has been positive, with 50% of patients changed to SC administration within 6 months of approval. A number of other patients have been identified for a change to SC TCZ within the next 6 months. While 1 patient subsequently elected to change back to IV TCZ, to date, no patient has come off SC TCZ due to an increase in disease activity. We hope to follow this study with a patient questionnaire to determine the patient perspective of changing to SC administration of TCZ. Conflicts of Interest The authors declare no conflicts of interest.

P07 Identifying the primary outcome measure and protocol components for a prospective feasibility study of corticosteroid regimens for CYP with JIA using consensus methods with young people, families and professionals

Abstract Background Juvenile idiopathic arthritis (JIA) is an umbrella term for seven relapsing-remitting inflammatory conditions in children and young people (CYP). Early, intensive treatment can prevent long-term damage; however, established drugs exhibit a delayed response, prompting the need for rapid-onset treatment in the form of corticosteroids. Given a lack of consensus as to which corticosteroid induction regimen should be used for CYP with JIA, a feasibility trial of different regimens is needed. The aim was to achieve consensus among CYP, families, and healthcare professionals (HCPs) about the primary outcome measures and protocol components to include in a prospective feasibility study. Methods A modified Nominal Group Technique was used to achieve consensus on the most appropriate primary outcome measure to be included in a prospective feasibility study, in addition to other protocol components such as inclusion/exclusion criteria. Fifteen participants participated in the process, including a combination of CYP with JIA, families (n = 9) and HCPs (n = 6). Results In the first vote, participants agreed that Juvenile Arthritis Disease Activity Score (JADAS) and Physician Global Assessment Score were most meaningful. During sub-group discussions, the need for a composite score which captured the voice of CYP and families was emphasised. In the second vote, JADAS and the JIA Core Set were identified as the most important. Further discussions led to the results of the third vote, agreeing JADAS as the primary outcome measure of choice being measured at 6 weeks after commencement of treatment. The majority of HCPs, CYP and families voted for all JIA sub-types to be included in a prospective feasibility study, with some queries about the inclusion of systemic JIA given its unique presentation. Participants also identified the need for more frequent data collection time points to capture the rapid onset of corticosteroid action, while CYP and families opted for accessible mechanisms for participation, such as digital follow-up strategies. Conclusion It is feasible to include CYP, families and HCPs in synthesising complex concepts to agree by consensus the design components of clinical research. The primary outcome measure for inclusion in a prospective feasibility study of corticosteroid regimens in CYP with JIA was co-prioritised, with CYP and families taking a leading role in the ultimate selection of an appropriate outcome measure and other study protocol components. Using consensus methods with CYP, families and HCPs is a systematic and rigorous way in which to select outcome measures that are both meaningful and relevant to everyone involved in the care and treatment of CYP with JIA. Conflicts of Interest The authors declare no conflicts of interest.

Prognosis, complications and treatment response in systemic juvenile idiopathic arthritis patients: A single-center experience.

Systemic juvenile idiopathic arthritis (sJIA) is a distinctive subtype of JIA characterized by systemic features and poor outcome. We aimed to investigate demographic and clinical features, long-term treatment response and disease complications in a large sJIA cohort. Patients diagnosed with sJIA followed up at a pediatric rheumatology outpatient department from January 2003 to December 2017 were included. Demographic and clinical features, long-term treatment response and disease complications were retrospectively collected. A total of 168 sJIA patients (51.8% female, 48.2% male) were included: 31.5% with monocyclic, 13.7% polycyclic and 54.8% with persistent clinical course. Corticosteroids were initially used in all patients. Methotrexate was used in 75% and cyclosporine A was used in 17.3% patients. Biological drugs were used in 42.8% patients; etanercept in 29.7%, anakinra in 16%, canakinumab in 16%, tocilizumab in 10% patients. Remission off medication was achieved in 82 (48.8%). Macrophage activation syndrome (MAS) was present in 11.9%, growth retardation in 11.3% patients. Eight percent (4/50) of patients had low bone mineral density. Three patients (1.78%) died due to MAS secondary multiorgan insufficiency and infection. The disease is characterized with diverse clinical presentation and possibly severe complications. MAS complicated with multiorgan insufficiency is the major mortality factor. Corticosteroids represent the mainstay of the initial treatment. In patients resistant to classic treatment, biological drugs should be timely introduced.

Serum Leucine-Rich α2-Glycoprotein as a Biomarker for Monitoring Disease Activity in Patients with Systemic Juvenile Idiopathic Arthritis.

To investigate whether serum leucine-rich α2-glycoprotein (LRG) levels are useful as a marker of disease activity in systemic juvenile idiopathic arthritis (s-JIA), we determined serum LRG levels in fifty-nine s-JIA patients, 15 with other subtypes of JIA, 7 with Kawasaki disease (KD), 7 with influenza A infection (flu), 7 with enterohemorrhagic Escherichia coli (EHEC) infection, and 20 healthy controls (HC). Results were compared with the clinical features of s-JIA and serum cytokine levels including interleukin- (IL-) 6, IL-18, and soluble tumor necrosis factor receptors I and II. Serum LRG levels in active s-JIA were higher compared to those in other subtypes of JIA, EHEC, flu patients, and HC. Serum LRG levels were normalized in the inactive s-JIA phase after treatment. Serum LRG levels were positively correlated with serum C-reactive protein and ferritin levels. Serum LRG levels reflected s-JIA disease activity and thus may be useful for monitoring s-JIA disease activity.

Body composition and phase angle as an indicator of nutritional status in children with juvenile idiopathic arthritis

BackgroundJuvenile idiopathic arthritis (JIA) is the most common chronic, systemic autoimmune connective tissue disease diagnosed in children and adolescents. An important aspect of monitoring of children with JIA is a precise assessment of the nutritional status to identify children and adolescents at risk of malnutrition. The aim of the study was to assess the body composition and phase angle in children diagnosed with JIA in comparison to age and sex matched healthy children since there are scarce reports in paediatric patients.MethodsA total of 46 children and adolescents aged 4–18 years, with JIA were included in the cross-sectional study. Controls were selected from the group of healthy children and adolescents. Children with diagnosed JIA and healthy children were strictly matched for age and gender. In both groups BIA with phase angle calculation was performed.ResultsPhase angle score was significantly lower in the study group compared to control group (5.45 ± 0.64 vs. 5.85 ± 0.80, p = 0.010). Also lower percentage of body cell mass (50.63 ± 3.46 vs. 52.70 ± 4.06, p = 0.010) and muscle mass (46.02 ± 6.32 vs. 49.53 ± 6.67, p = 0.005) were revealed. In the analysis of subtypes of JIA we found significant differences between children and adolescents with polyarthritis compared to control group, while no significant differences were found between patients with oligoarthritis and control group.ConclusionsThe obtained results indicate a higher risk of malnutrition in children and adolescents with JIA compared to healthy peers, predominantly in patients with polyarthritis.

Association between interleukin-10 polymorphisms and juvenile idiopathic arthritis: a meta-analysis

The aim of this review is to investigate IL-10 polymorphisms (-1082 G/A, -819 C/T, and -592 C/A) and their association with susceptibility to JIA. A meta-analysis was conducted after database search for relevant articles (MEDLINE and EMBASE). A total of seven studies involving 1495 patients and 1670 controls were considered in the meta-analysis. There was no association between the IL-10 -1082 G/A, -819 C/T, and -592 C/A polymorphisms and JIA in allele contrast and any of the genetic models (allele contrast: odds ratio [OR] 0.90, 95% confidence interval [CI] 0.79-1.02, P=0.09; OR=0.97, 95% CI 0.83-1.13, P=0.68; OR=0.92, 95% CI 0.81-1.06, P=0.24, respectively). In subgroup analysis, none of the subtypes of JIA including systemic, rheumatoid factor (RF)-positive polyarticular, RF-negative polyarticular, and oligoarticular was not significantly associated with IL-10 polymorphism. Meta-analysis of the IL-10 haplotype revealed no association between GCC, ACC, and ATA haplotypes and JIA. This meta-analysis showed that IL-10 polymorphisms were not associated with risk of JIA.

Conventional radiography in juvenile idiopathic arthritis: Joint recommendations from the French societies for rheumatology, radiology and paediatric rheumatology

BackgroundJuvenile idiopathic arthritis (JIA) can cause structural damage. However, data on conventional radiography (CR) in JIA are scant.ObjectiveTo provide pragmatic guidelines on CR in each non-systemic JIA subtype.MethodsA multidisciplinary task force of 16 French experts (rheumatologists, paediatricians, radiologists and one patient representative) formulated research questions on CR assessments in each non-systemic JIA subtype. A systematic literature review was conducted to identify studies providing detailed information on structural joint damage. Recommendations, based on the evidence found, were evaluated using two Delphi rounds and a review by an independent committee.Results74 original articles were included. The task force developed four principles and 31 recommendations with grades ranging from B to D. The experts felt strongly that patients should be selected for CR based on the risk of structural damage, with routine CR of the hands and feet in rheumatoid factor-positive polyarticular JIA but not in oligoarticular non-extensive JIA.ConclusionThese first pragmatic recommendations on CR in JIA rely chiefly on expert opinion, given the dearth of scientific evidence. CR deserves to be viewed as a valuable tool in many situations in patients with JIA.Key Points• CR is a valuable imaging technique in selected indications.• CR is routinely recommended for peripheral joints, when damage risk is high.• CR is recommended according to the damage risk, depending on JIA subtype.• CR is not the first-line technique for imaging of the axial skeleton.

Genetics: Subtype of JIA is genetically similar to adult RA.

Genetics: Subtype of JIA is genetically similar to adult RA.

Time to diagnosis in juvenile idiopathic arthritis: a french perspective

BackgroundJuvenile idiopathic arthritis (JIA) is a rare disease that is not widely known by paediatricians and general practitioner (GP) leading to diagnostic error and delayed care provision. We aimed to analyse patient’s journey and time to diagnosis of JIA (delay from the first symptom to the diagnosis of JIA).We performed a retrospective cohort study of 67 patients diagnosed with JIA and seen in the paediatric rheumatology department of the Kremlin Bicêtre Hospital, between July 2002 and January 2015. Patients were selected for analysis in order to represent an equal distribution of five JIA subtypes: oligoarticular onset (21), polyarticular onset (13), enthesitis-related arthritis (17), and systemic onset (16).ResultsSixty-seven patients were finally analysed (42 girls). Before JIA diagnosis was made, patients had visited a mean of three physicians (3.6 ± 1.4 (mean; SD)). Emergency room physicians (52%) were the first patient’s referral before GP (42%). Paediatric rheumatologists were mostly seen as third referral (52% versus 3% at first referral). Reactive arthritis (34%) and septic arthritis (24%) represented both the most common initial diagnosis. JIA was suspected after an average median time delay of 3 months (0.26–81.2) except for 25 patients (37%): SJIA (n = 9), ERA (n = 7), OAJIA (3) and POJIA (n = 6) for whom diagnosis was suspected straightaway. In most cases (88%), JIA was established by paediatric rheumatologists.Surprisingly, the median total time to diagnosis in our population was rather short (3 months). Paediatric rheumatologist played a major role in making the diagnosis but the journey to reach them was long and complex with multiple referrals. These results reinforce the necessity of improving GP and emergency physician’s awareness and education on paediatric rheumatic diseases as the importance of a strong network in paediatric rheumatology to improve patient’s level of care.ConclusionWe highlighted the complex patient’s journey to diagnosis in children with JIA and made assumptions that reference center might reduce time to diagnosis although not statically proven. Further analysis with a larger number of patients might be needed to better investigate this probability.

Efficacy of Tocilizumab in the Treatment of Systemic Onset Juvenile Idiopathic Arthritis

Background: Systemic JIA (sJIA) is the most severe sub type of JIA with limited treatment option and responsible for most of the disability and morbidity in JIA.Objective: To assess the efficacy of Tocilizumab (TCZ) in refractory sJIA patients according to disease activity score in 28 joint criteria.Methodology: This interventional study was carried in the department of Paediatrics, Bangabandhu Sheikh Mujib Medical University (BSMMU). A total number of 22 sJIA patients who were refractory to traditional DMARDs were offered TCZ. Among them 15 patients agreed to take TCZ (cases) and 7 patients did not (controls). All the cases and controls were assessed according to DAS 28 criteria at enrollment, 12 weeks and 24 weeks of TCZ therapy. DAS 28 scores during assessment were compared.Results: After TCZ therapy systemic features subsided and laboratory features improved in 100% cases. Among cases 93.3% and 92.3% had moderate response at 12 and 24 weeks respectively according to DAS 28 criteria. Among controls 71.5% and 85.7% had moderate response at 12 and 24 weeks respectively (p0.001). Among cases 40% and 60% patients achieved remission at 12 and 24 weeks, where as among controls none achieved remission. Dose of steroid was significantly reduced among cases but was increased significantly among controls. Few side effects like pharyngitis, Varicella, septicemia, anaphylactoid reaction and raised ALT were observed.Conclusion: Tocilizumab therapy was effective according to DAS 28 criteria refractory sJIA.Bangladesh J Child Health 2015; VOL 39 (3) :129-134

Paediatric rheumatology clinic population in Southeast Asia: are we different?

To examine the descriptive epidemiology of the patient population referred to paediatric rheumatology centres (PRCs) in Southeast Asia (SEA) and to compare the frequency of conditions encountered with other PRC populations. A web-based Registry for Childhood Onset Paediatric Rheumatic Diseases was established in 2009 and seven PRCs in four SEA countries, where paediatric rheumatologists are available, participated in a prospective 24 month data collection (43 months for Singapore). The number of patients analysed was 4038 (788 from Malaysia, 711 from the Philippines, 1943 from Singapore and 596 from Thailand). Over 70% of patients evaluated in PRCs in Malaysia, the Philippines and Thailand had rheumatic diseases (RDs), as compared with one-half of the proportion seen in Singaporean PRCs, which was similar to the Western PRC experience. Among RDs diagnosed (n = 2602), JIA was the most common disease encountered in Malaysia (41%) and Thailand (61%) as compared with systemic vasculitides in the Philippines (37%) and Singapore (35%) among which Henoch-Schönlein purpura was the most prevalent. SLE and related diseases were more common, but idiopathic pain syndrome and abnormal immunological laboratory tests were rarer than those seen in the West. JIA subtype distributions were different among countries. Among non-RDs (n = 1436), orthopaedic and related conditions predominated (21.7-59.4%). The frequencies of RDs seen by SEA PRCs were different from those in the West. Systemic vasculitides and SLE were common in addition to JIA. Paediatric rheumatologist availability and healthcare accessibility partially explain these observed discrepancies.

Genetic architecture distinguishes systemic juvenile idiopathic arthritis from other forms of juvenile idiopathic arthritis: clinical and therapeutic implications

ObjectivesJuvenile idiopathic arthritis (JIA) is a heterogeneous group of conditions unified by the presence of chronic childhood arthritis without an identifiable cause. Systemic JIA (sJIA) is a rare form of...

Descripción de una cohorte de pacientes de artritis idiopática juvenil en el estado de Sonora, México

IntroductionJuvenile idiopathic arthritis (JIA) is one of the most common childhood chronic degenerative diseases causing serious sequelae such as disability and blindness with clinical course, prognosis and treatment for all different phenotypes. ObjectiveTo determine the most common clinical subtypes of JIA in the rheumatology of a second level hospital care in northwestern Mexico. Material and methodsUnder a cohort design were studied patients with JIA in rheumatology service. The classification into subtypes of the disease was performed by clinical and laboratory criteria issued by the ILAR. The frequency of the subtypes of JIA, as well as the latter's association with sociodemographic variables such as age and gender was measured. ResultsFrom 35 patients with JIA predominance of female gender was 74% of the cases studied. The most affected age group was observed in patients between 10 and 12, most frequent subtypes was arthritis associated with enthesitis (40%) and poly articular JIA with positive rheumatoid factor (20%). Significant association between age and gender and gender cases and subtype of JIA found. ConclusionsJIA cases presented at an earlier age in the male gender, unlike girls in wich age presentation comes between 10 and 12 years.

Review of biomarkers in systemic juvenile idiopathic arthritis: helpful tools or just playing tricks?

BackgroundDiagnosing systemic juvenile idiopathic arthritis (SJIA) can be extremely challenging if typical arthritis is lacking. A variety of biomarkers have been described for the diagnosis and management of SJIA. However, very few markers have been well-validated. In addition, increasing numbers of biomarkers are identified by high throughput or multi-marker panels.MethodWe identified diagnostic or prognostic biomarkers by systematic literature review, evaluating each according to a predefined level of verification, validation or clinical utility. Diagnostic biomarkers were those identifying SJIA versus (1) non-SJIA conditions or healthy controls (HC) or (2) other non-systemic JIA subtypes. Prognostic biomarkers were those specifically tested for the prediction of (1) disease flare, (2) increased disease activity +/- discrimination of active versus inactive disease, or (3) macrophage activation syndrome (MAS).ResultsFifty-five studies fulfilled the inclusion criteria identifying 68 unique biomarkers, of which 50/68 (74 %) were investigated by only a single research group. Candidate marker verification and clinical utility was evaluated according to whether markers were readily and reliably measurable, investigated by independent study groups, discovered by more than one method (i.e. verified markers) and validated in independent cohorts. This evaluation revealed diagnostic biomarkers of high interest for further evaluation in the diagnostic approach to SJIA that included heme oxygenase-1, interleukin-6 (IL-6), IL-12, IL-18, osteoprotegerin, S100 calcium-binding protein A12 (S100A12) and S100A8/A9.ConclusionIn summary, a number of biomarkers were identified, though most had limited evidence for their use. However, our findings combined with the identified studies could inform validation studies, whether in single or multi-marker assays, which are urgently needed.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-1069-z) contains supplementary material, which is available to authorized users.

Plasma miR-26a as a Diagnostic Biomarker Regulates Cytokine Expression in Systemic Juvenile Idiopathic Arthritis.

We sought to identify specific microRNA (miRNA) for systemic juvenile idiopathic arthritis (sJIA) and to determine the involvement of these miRNA in regulating the expression of cytokines. Microarray profiling was performed to identify differentially expressed miRNA in sJIA plasma. Levels of candidate miRNA and mRNA were assessed by real-time PCR, and cytokines were measured by ELISA. Dual-luciferase reporter assay was used to validate the direct interaction between miR-26a and interleukin 6 (IL-6). Forty-eight miRNA were differentially expressed in the plasma of patients with sJIA compared with healthy controls (HC). Five miRNA were selected for further validation. The expression level of miR-26a was exclusively elevated in the plasma of patients with sJIA as compared with 4 rheumatic diseases and 2 subtypes of JIA (oligoarticular and polyarticular). The levels of IL-6, IL-1β, and tumor necrosis factor-α in the plasma of patients with sJIA were increased, and only IL-6 presented a positive correlation with miR-26a (r = 0.539, p < 0.0001). After stimulation with IL-6, miR-26a expression was upregulated in THP-1 cells, while the supernatant level of IL-6 was downregulated by transfection of miR-26a mimics. Consistently, direct target relationship between miR-26a and IL-6 was confirmed. This study demonstrates that miR-26a is expressed specifically and highly in sJIA plasma and suggests that miR-26a may regulate the levels of cytokines in sJIA. Our findings highlight miR-26a as a potential biomarker for the diagnosis as well as differential diagnosis of sJIA.

The Pattern of Juvenile Idiopathic Arthritis in a Single Tertiary Center in Saudi Arabia.

Introduction. Juvenile Idiopathic Arthritis (JIA) is the most common chronic arthritis in children. Our aim is to describe demographic, clinical, and laboratory characteristics and treatment of JIA patients followed up in Pediatric Rheumatology clinic in a tertiary center in Saudi Arabia. Methods. Medical records of all patients who are followed up between January 2007 and January 2015 were retrospectively reviewed. Data were collected about demographic, clinical, and laboratory features and treatment. Results. Total patients were 82, males were 31 (37.8%), and mean age of JIA onset was 7.1 ± 3.6 yr. Mean follow-up duration was 2.67±1.6 yr. Systemic onset JIA (SoJIA) was the commonest (36.5%), followed by polyarticular in 29.2% and oligoarticular in 28%. Large and small joints are involved in 76 (92%) and 30 (36.6%), respectively. Main extra-articular feature was fever in 34 (41.4%). Uveitis was diagnosed in 7 (8.5%) and in 5 (21.7%) of oligoarticular JIA. Anemia was found in 49 (59.7%), high ESR in 45 (54.8%), and leukocytosis and thrombocytosis in 33 (40.2%). Positive ANA was found in 30 (36.5%) mainly in oligoarticular subtype as 12 (52%) patients (out of 23) had this positive test. 9 patients (10.9%) required NSAIDs only, 6 patients (7.3%) required NSAIDs and intra-articular steroids only, and 19 (23%) required NSAIDs, methotrexate, steroids, and biologics. Conclusion. SoJIA is the most common JIA subtype in our study. A population based rather than a single center study will give more details about JIA characteristics in Saudi Arabia

Effectiveness and long-term retention of anti-tumour necrosis factor treatment in juvenile and adult patients with juvenile idiopathic arthritis: data from Reuma.pt.

Assess the effectiveness and safety of biologic therapy as well as predictors of response at 1 year of therapy, retention rate in biologic treatment and predictors of drug discontinuation in JIA patients in the Portuguese register of rheumatic diseases. We prospectively collected patient and disease characteristics from patients with JIA who started biological therapy. Adverse events were collected during the follow-up period. Predictors of response at 1 year and drug retention rates were assessed at 4 years of treatment for the first biologic agent. A total of 812 JIA patients [65% females, mean age at JIA onset 6.9 years (s.d. 4.7)], 227 received biologic therapy; 205 patients (90.3%) were treated with an anti-TNF as the first biologic. All the parameters used to evaluate disease activity, namely number of active joints, ESR and Childhood HAQ/HAQ, decreased significantly at 6 months and 1 year of treatment. The mean reduction in Juvenile Disease Activity Score 10 (JADAS10) after 1 year of treatment was 10.4 (s.d. 7.4). According to the definition of improvement using the JADAS10 score, 83.3% respond to biologic therapy after 1 year. Fourteen patients discontinued biologic therapies due to adverse events. Retention rates were 92.9% at 1 year, 85.5% at 2 years, 78.4% at 3 years and 68.1% at 4 years of treatment. Among all JIA subtypes, only concomitant therapy with corticosteroids was found to be univariately associated with withdrawal of biologic treatment (P = 0.016). Biologic therapies seem effective and safe in patients with JIA. In addition, the retention rates for the first biologic agent are high throughout 4 years.

No association of IL-12p40 pro1.1 polymorphism with juvenile idiopathic arthritis.

BackgroundIL-12p40 plays an important role in the activation of the T-cell lines like Th17 and Th1-cells. Theses cells are crucial in the pathogenesis of juvenile idiopathic arthritis. A polymorphism in its promoter region and the genotype IL12p40 pro1.1 leads to a higher production of IL-12p40. We studied whether there is a difference in the distribution of the genotype in patients with JIA and the healthy population.MethodsIn 883 patients and 321 healthy controls the IL-12p40 promoter genotype was identified by ARMS-PCR.ResultsThere is no association of IL-12p40 pro polymorphism neither in patients with JIA compared to controls nor in subtypes of JIA compared to oligoarthritis. We found a non-significant tendency of a higher prevalence of the genotype pro1.1 in systemic arthritis (32.4 %) and in rheumatoid factor negative polyarthritis (30.5 %) and a lower pro1.1 genotype in persistent oligoarthritis (20.7 %) and in enthesitis-related arthritis (17 %). Likelihood of the occurrence of genotype IL12-p40 pro1.1 in patients with systemic arthritis (OR 1.722, CI 95 % 1.344-2.615, p 0.0129) and RF-negative polyarthritis (OR 1.576, CI 95 % 1.046-2.376, p 0.0367) compared to persistent oligoarthritis was significantly higher. This was also true for comparison of their homozygous genotypes IL-12p40 pro 1.1 and 2.2 in systemic arthritis (OR 1.779, CI 95 % 1.045-3.029, p 0.0338). However, in Bonferroni correction for multiple hypothesis this was not significant.ConclusionA tendency of a higher prevalence of the genotype IL-12p40 pro1.1 in systemic arthritis and in rheumatoid factor negative polyarthritis was observed but not significant. Further investigations should be done to clarify the role IL-12p40 in the different subtypes of JIA.

Increased carotid artery intima-media thickness and myeloperoxidase level in children with newly diagnosed juvenile idiopathic arthritis.

IntroductionJuvenile idiopathic arthritis (JIA) is a frequent childhood rheumatic disease characterized by chronic inflammation. The latter has been related to impairment of arterial functional-structural properties, atherogenesis and later cardiovascular events. The objective of this study was to examine intima-media thickness (IMT) and the parameters of arterial stiffness in children with JIA at diagnosis and their correlation with JIA subtype and markers of inflammation and atherosclerosis.MethodsThirty-nine newly diagnosed patients with JIA (26 girls; mean age, 13.2 ± 2.6 years) and 27 healthy controls (9 girls; mean age, 13.6 ± 3.4 years) were included in the study. Twelve patients had oligoarthritis, fifteen had extended oligoarthritis and twelve had rheumatoid factor–negative polyarthritis. IMT of the common carotid artery was determined by ultrasonography, carotid-femoral pulse wave velocity (cfPWV) and augmentation index adjusted to a heart rate of 75 beats/min (AIx@75) were determined by applanation tonometry. The serum levels of atherosclerosis-related biomarkers, such as asymmetric dimethylarginine (ADMA), myeloperoxidase (MPO) and adiponectin, were measured by enzyme-linked immunosorbent assay.ResultsMean IMT (0.46 ± 0.04 vs. 0.42 ± 0.04 mm; p = 0.0003) and MPO concentration (115.2 [95 % confidence interval {95 % CI}, 97.4–136.3] vs. 57.6 [95 % CI, 47.1–70.3] ng/ml; p < 0.0001) were higher in the patients with JIA than in the control subjects. The cfPWV, AIx@75 and serum ADMA and adiponectin levels did not significantly differ between the groups and JIA subtypes. Serum adiponectin level correlated negatively with AIx@75 in patients with JIA (r = −0.38; p < 0.05).ConclusionsPatients with JIA have increased mean IMT and elevated MPO levels at early stages of the disease. AIx@75 was inversely independently associated with adiponectin level in the patients, suggesting that lower adiponectin levels might influence arterial subclinical stiffening in patients with newly diagnosed JIA.

Meta-analysis: diagnostic accuracy of anti-cyclic citrullinated peptide antibody for juvenile idiopathic arthritis.

Objective. To estimate the diagnostic accuracy of the anti-CCP test in JIA and to evaluate factors associated with higher accuracy. Methods. Two investigators performed an extensive search of the literature published between January 2000 and January 2014. The included articles were assessed by the Quality Assessment of Diagnostic Accuracy Studies tool. The meta-analysis was performed using a summary ROC (SROC) curve and a bivariate random-effect model to estimate sensitivity and specificity across studies. Results. The bivariate meta-analysis yielded a pooled sensitivity and specificity of 10% (95% confidence interval (CI): 6.0%–15.0%) and 99.0% (95% CI: 98.0%–100.0%). The area under the SROC curve was 0.96. Sensitivity estimates were highly heterogeneous, which was partially explained by the higher sensitivity in the rheumatoid factor-positive polyarthritis (RF+ PA) subtype (48.0%; 95% CI: 31.0%–65.0%) than in the other subtypes (17.0%; 95% CI: 14.0%–20.0%) and the higher sensitivity of the Inova assay (17.0%; 95% CI: 14.0%–20.%%) than the other assays (0.05%; 95% CI: 2.0%–11.0%). Conclusions. Anti-CCP antibody test has a high specificity for the diagnosis of JIA. The sensitivity of this test is low and varies across populations but is higher in RF+ PA than in other JIA subtypes.