Analysis of childhood reactive arthritis and comparison with juvenile idiopathic arthritis

There is currently no agreement on how to classify and diagnose reactive arthritis (ReA) and what kind of clinical and laboratory findings are specific for the diagnosis. This study retrospectively analyzed the initial clinical manifestations and laboratory findings in children diagnosed with ReA and juvenile idiopathic arthritis (JIA). A comparison was also made between these two groups to see if there were differences. A retrospective chart review was performed and 44 patients diagnosed with ReA and 80 patients with JIA were enrolled in this study. Their initial clinical manifestations and laboratory findings were also analyzed and compared. The initial clinical manifestations in ReA were analyzed including the demographic data, the preceding infection history, the duration of the infectious episode to the onset of arthritis, the duration of arthritic symptoms, and the involved joint pattern. Comparison of the initial laboratory findings between patients with ReA and JIA showed significant differences between erythrocyte sedimentation rates (ESR) in the first hour, platelet counts (p<0.05), and ESR in the second hour (p=0.052). Further, comparing ReA with the subtypes of JIA, significant differences were noted between ReA and the systemic type in terms of hemoglobin level, platelet counts, C-reactive protein, and first and second hour ESR (p<0.05). However, if compared with the polyarticular or pauciarticular type, only the platelet counts showed any significant statistical difference (p<0.05). This study summarizes clinical experiences in ReA. The differences in laboratory findings of ReA and JIA may provide a clue in making a differential diagnosis.     

Hip involvement in juvenile idiopathic arthritis

We analyzed the clinical, biological, and radiological aspects of hip involvement in juvenile idiopathic arthritis (JIA) in a developing country. The recruited patients fulfilled the International League Against Rheumatism criteria for the diagnosis of the JIA. Clinical, biological, and radiological parameters relating to the JIA were collected. Hip involvement was assessed according to clinical and radiological data related to hip disease. One hundred twenty-one patients were included (68 girls and 53 boys). The mean age of the disease onset was 9 ± 4.2 years (1–16 years).The mean age of the patients at the time of the study was 15 ± 10 years (2–46 years). The duration of the disease was 5 ± 8.5 years (0.5–39 years). Forty cases (33%) of the hip involvement were noted. The mean age was 24 ± 10.03 years (3–46 years); the sex ratio was 1:3. The mean duration of the hip disease was 0.6 ± 3.6 years (3–14 years). Hip arthritis seemed to be more frequent in polyarticular and enthesitis-related arthritis. The severity of the hip involvement was significantly correlated with early disease onset, disease duration, subtypes, and high disability (for all these data p < 0.05). This study suggested that in JIA hip involvement was more frequent in enthesitis-related arthritis and polyarticular subtypes. It was correlated with the severity and the early disease onset of the JIA, which was similar to reported data.     

Differential plasma microRNAs expression in juvenile idiopathic arthritis

Objectives. To identify potential novel biomarkers for juvenile idiopathic arthritis (JIA), we evaluated the correlation between plasma expression levels of specific miRNAs and disease characteristics of JIA.

Methods. Differentially expressed miRNAs in JIA plasma were identified by microarray analysis. Five candidate plasma miRNAs with differential expression were further evaluated by qRT-PCR. The correlation between the expression of candidate plasma miRNAs and clinical parameters of JIA patients was assessed.

Results. The expression of miR-16, miR-146a, and miR-223 was higher, and miR-132 was lower, in the plasma of JIA patients as compared with healthy subjects and juvenile ankylosing spondylitis patients (p < 0.05). Plasma miR-16 concentrations were considerably higher for polyarticular JIA patients than oligoarticular JIA patients and correlated with the juvenile arthritis magnetic resonance imaging scores for the hip and plasma interleukin-6 or IL-6 levels. Additionally, miR-146a levels correlated directly with the Juvenile Arthritis Disease Activity Scores in 27 joints, the swollen joint count, the limited joint count, and the juvenile arthritis magnetic resonance imaging scores for the hip, but correlated inversely with plasma tumor necrosis factor-α or TNF-α levels.

Conclusions. This study demonstrates that the expression of plasma miRNAs correlates with JIA disease and suggests that plasma miR-16 and miR-146a have potential novel value for JIA diagnosis.     

Anticyclic citrullinated peptide antibodies in juvenile idiopathic arthritis

Anticyclic citrullinated peptide (anti-CCP) antibodies have been detected in patients with juvenile idiopathic arthritis (JRA), particularly in those with polyarticular JIA. We analyzed the presence of anti-CCP antibodies of the IgG class in sera of patients with defined juvenile idiopathic arthritis (JIA) of various subgroups. One hundred and fifty-nine serum samples were investigated. Forty-five patients were diagnosed with JIA (15 male and 30 female) aged 1.9–17.3 years (median 12.9, mean 11.0). Thirty-eight samples were taken from patients suffering from other autoimmunopathies and 34 patients with other underlying diseases were taken at different time points in their disease course. Under 42 samples were taken from patients with noninflammatory diseases. Enzyme-linked immunosorbent assay (ELISA) was used for the detection of anti-CCP antibodies. Anti-CCP antibodies were found in 6.9% of all samples and in 4.4% patients with JIA. Disease duration and medication did not differ significantly between anti-CCP positive and negative patients. A review of the literature and our own results shows that anti-CCP antibodies can be detected in the sera of only some patients with JIA. Routine determination of anti-CCP cannot be recommended.     

Anticyclic citrullinated peptide antibodies in juvenile idiopathic arthritis

Abstract

Anticyclic citrullinated peptide (anti-CCP) antibodies have been detected in patients with juvenile idiopathic arthritis (JRA), particularly in those with polyarticular JIA. We analyzed the presence of anti-CCP antibodies of the IgG class in sera of patients with defined juvenile idiopathic arthritis (JIA) of various subgroups. One hundred and fifty-nine serum samples were investigated. Forty-five patients were diagnosed with JIA (15 male and 30 female) aged 1.9–17.3 years (median 12.9, mean 11.0). Thirty-eight samples were taken from patients suffering from other autoimmunopathies and 34 patients with other underlying diseases were taken at different time points in their disease course. Under 42 samples were taken from patients with noninflammatory diseases. Enzyme-linked immunosorbent assay (ELISA) was used for the detection of anti-CCP antibodies. Anti-CCP antibodies were found in 6.9% of all samples and in 4.4% patients with JIA. Disease duration and medication did not differ significantly between anti-CCP positive and negative patients. A review of the literature and our own results shows that anti-CCP antibodies can be detected in the sera of only some patients with JIA. Routine determination of anti-CCP cannot be recommended.     

Articular damage in adults with juvenile idiopathic arthritis

The goal of this study was to assess the long-term articular damage in adults with juvenile idiopathic arthritis (JIA) using the Rheumatoid Arthritis Articular Damage (RAAD) score and to determine any associations between the disease-related parameters and RAAD score. Thirty-eight adults identified with JIA at 18 years of age or older with disease duration of at least 5 years were assessed by means of the RAAD score. Patients were divided into three groups according to disease duration as 5-10 years (group 1), 11-15 years (group 2) and more than 16 years (group 3), and into three groups according to JIA subtypes as seropositive polyarticular (group A), seronegative polyarticular (group B), and oligoarticular (group C). Functional disability, functional status, disease activity and depression were measured by Health Assessment Questionnaire (HAQ), Steinbrocker classification, Disease Activity Score 28 (DAS 28), and Beck Depression Inventory, respectively. We investigated any possible associations between the RAAD score and groups, sex, age at onset of the disease, HAQ, Steinbrocker classification, DAS 28, and Beck Depression Inventory. We observed significant differences in RAAD scores according to groups A, B, C (p < 0.01), but not according to groups 1, 2, 3 or sex (p > 0.05). While the RAAD score correlated well with HAQ (p < 0.001), Steinbrocker classification (p < 0.001) and DAS 28 (p < 0.01), it did not correlate with age at onset of the disease (p > 0.05) or Beck Depression Inventory (p > 0.05). Seropositive polyarticular patients demonstrate the worst articular damage scores. Even though articular damage does not progress over time and JIA frequently has a benign course, care should be given to establishing regular follow-up periods and well-arranged treatments, especially for seropositive polyarticular groups, to maintain satisfactory long-term disease outcome throughout the lives of JIA patients.     

Serological screening for coeliac disease in patients with juvenile idiopathic arthritis

Background and study aimsJuvenile idiopathic arthritis (JIA) is characterized by autoimmune aetiology. A gene locus 4q27 related to rheumatoid arthritis, psoriatic arthritis, and coeliac disease is associated with susceptibility to JIA. There are reports indicating several patients with JIA had been diagnosed with CD. We aimed to assess the frequency of coeliac disease (CD) in patients with juvenile idiopathic arthritis (JIA).Patients and methodsThis prospective study was carried out from October 2015 to August 2016 and included 96 patients with JIA. All patients were evaluated in terms of clinical and laboratory findings of CD. Levels of total IgA and tissue transglutaminase antibody (tTG) IgA were measured in all patients. Those with increased level of tTG IgA were further tested for anti-endomysium IgA antibodies (EMA). Gastroduodenoscopy were planned for a definite diagnosis of CD in patients with positive EMA.ResultsOf the 96 patients in our study, 34 (35.4%) had oligoarticular form of JIA, 29 (30.2%) had polyarticular form, 12 (12.5%) had ERA form, 11 (11.5%) had systemic form, and 10 (10.4%) had psoriatic form. Sixteen of our patients (16.6%) were not using any drugs during the study. Neither EMA IgA antibodies were analysed nor gastro-duodenoscopy was performed because no patients were positive for tTG IgA. There was no difference in terms of tTG levels between the patients using NSAIDs or other drugs.ConclusionWe did not find CD in children with JIA. Long term studies with more JIA patients are needed to provide more precise interpretation.     

Antinuclear antibody-positive cohort constitutes homogeneous entity in juvenile idiopathic arthritis

Objective. To identify a homogeneous entity for antinuclear antibody (ANA)-positive patients suffering from juvenile idiopathic arthritis (JIA).

Methods. All of the clinical features were recorded retrospectively. ANA positivity was defined as more than twice positive results at a titer of > 1:100. The correlation between ANA positivity and clinical parameters was assessed by multiple logistic regression analysis.

Result. Of 120 patients, 49 patients were ANA positive (31 oligoarthritis, 18 rheumatoid factor [RF]-negative polyarthritis) and 71 patients were ANA negative (48 oligoarthritis, 23 RF-negative polyarthritis), and were recruited retrospectively to this study according to the International League of Associations for Rheumatology (ILAR) criteria. In ANA-positive cohort, the characteristics of early-onset age, female predominance, and asymmetric arthritis were observed compared with ANA-negative cohort including oligoarthritis and RF-negative polyarthritis. Correspondingly, we found that ANA-positive cohort had higher cumulative number of joints affected at 9 and 12 months after disease presentation than ANA-negative cohort, had lower frequency of occurrence of image change, and had a different pattern of affected arthritis than ANA-negative cohort, which was more likely to have knee involvement and less likely to have hip and shoulder involvement. ANA positivity correlated strongly with asymmetric arthritis, female predominance and wrist involvement.

Conclusion. This study demonstrates that ANA-positive cohort divided into different subgroups by present ILAR criteria share the similar features and suggests that ANA positivity might serve as a novel potential value for JIA classification.     

Therapeutic advancements in juvenile idiopathic arthritis

The treatment of juvenile idiopathic arthritis (JIA) has substantially evolved over the past two decades. Research has been conducted and is ongoing on how therapies can best be utilized either as monotherapy or in combination for enhanced efficacy. The introduction of biologic therapies that selectively target specific cytokines has changed the acceptable clinical course of childhood arthritis. In addition to the development and utilization of new therapeutic agents, the pediatric rheumatology community has made vital progress toward defining disease activity, developing validated outcome measures, and establishing collaborative networks to assess both clinical outcomes and the long-term side effects related to therapeutics for juvenile arthritis. In this chapter, we will discuss the therapeutic evolution in JIA over the past two decades. Although the largest strides have been made with biologic agents, and these newer drugs have more rigorous data to support their use, select commonly used non-biologic therapies are included, with the discussion focused on more recent updated literature.     

Nitric oxide levels and the severity of juvenile idiopathic arthritis

In this study, we evaluate the distribution of nitric oxide (NO) in the serum of juvenile idiopathic arthritis (JIA) patients, correlating it with parameters of the severity of the disease. Ninety-seven patients with mean age 11.7 years and disease duration 4.8 years, showing active disease or not, grouped as oligoarticular (n = 34), polyarticular (n = 29) and systemic (n = 34) group, presenting uveitis and positive RF with erosive arthritis or active disease and erosions had significantly high levels of NO than the inactive ones. NO correlated with TNF-α in the oligoarticular subtype (P < 0.03), with pain in the polyarticular subtype with active disease (P < 0.04) and with ESR in the systemic subtype with active disease (P < 0.03). TNF-α concentration was high in all patients with active disease, accompanying NO production. The data confirm the production of NO in JIA patients, indicating a possible positive correlation between the production of NO and severity of the disease.     

Interleukin-18 as a mediator of systemic juvenile idiopathic arthritis

The objective of this report is to explore the balance between serum and synovial fluid levels of interleukin (IL)-18 in children with juvenile idiopathic arthritis (JIA). Blood samples were obtained from 81 children with JIA and 18 control children. Synovial fluid samples were collected from 16 children with oligoarticular JIA. Concentrations of IL-18 were determined using commercial kit. Patients with systemic JIA had higher serum levels of IL-18 than patients with other forms of JIA or control children, both during the active (median, range: 6,240, 1,600–78,750 pg/ml) and inactive (1,615, 513–3,270 pg/ml) phase of disease [analysis of variance (ANOVA), P < 0.05). Levels of IL-18 in sera of children with oligoarticular JIA (255, 89–4,342 pg/ml) were similar to the respective synovial fluid levels (217, 89–1,245 pg/ml). Serum levels of IL-18 were proportional to the erythrocyte sedimentation rate and levels of C-reactive protein, but inversely proportional to the haemoglobin levels. IL-18 appears to be an important mediator of systemic JIA, while it seems of a lesser relevance in pathogenesis of other JIA forms. Therefore, inhibition of IL-18 might be a base for a successful biological therapy for systemic JIA.     

Chitotriosidase as a marker of disease activity in sarcoidosis

Sarcoidosis is a chronic granulomatous inflammation. The clinical spectrum in childhood is heterogeneous. Angiotensin converting enzyme (ACE) activity is used as a marker for disease activity. Human chitotriosidase is produced in macrophages. In this study serum chitotriosidase levels were significantly higher in active sarcoidosis, than in inactive disease or healthy controls. Serum chitotriosidase concentrations may be a useful marker for monitoring disease activity in sarcoidosis.     

幼年特发性关节炎诊疗规范

幼年特发性关节炎(JIA)临床上常见亚型包括全身型JIA、少关节型/多关节型JIA和幼年脊柱关节炎。本病无特异性诊断指标, 需与感染性疾病和恶性病相鉴别。全身型JIA起病多急骤, 病情进展快, 易合并巨噬细胞活化综合征而危及生命。儿童风湿科医生对JIA的诊断及治疗经验仍不足, 规范化诊疗水平有待进一步提高。中华医学会风湿病学分会组织有关专家, 在借鉴国内外诊疗规范和分类标准的基础上, 制定本规范, 旨在规范JIA各亚型及全身型JIA合并巨噬细胞活化综合征的诊断和治疗方案, 以降低致死率和严重并发症的发生率, 从而改善患儿预后。     

Role of MRI in evaluation of hip joint involvement in juvenile idiopathic arthritis

Aim of the WorkTo evaluate the role of MRI in diagnosing hip arthritis and correlating it with clinical and laboratory assessments in juvenile idiopathic arthritis (JIA).Patients and MethodsThe study included 30 patients with JIA with mean age of 13.5 ± 4.5. Disease activity was evaluated by DAS28 score, physician’s global assessment (PGA–VAS), patient’s global assessment (VASglobal) and the assessment of functional ability by (CHAQ). Hip joint evaluation was assessed by hip pain on movement and the degree of limitation of motion (score 0–3). Plain radiography and MRI of the hip joint were performed for all patients. MRI score was done.ResultsMRI of hips was abnormal in 12 (40%) of all patients: 2/8 (25%) of the oligoarticular group, 4/13 (30.8%) of the polyarticular group, 5/7 (71.4%) of the systemic onset group and 1/2(50%) of the enthesitis related group. Comparing mean values of MR scores of the four clinical subsets showed significant difference (p < 0.001). Patients with active disease showed higher MR scores (3.7 ± 1.5) than those with inactive disease (2.1 ± .9) [p < 0.002]. Presence of effusion and gadolinium enhancement were significantly higher in active hips (p < 0.01 and p < 0.001 respectively). VAS–PGA and ESR were significantly correlated with MRI score (p < 0.02 and <0.05 respectively).ConclusionMRI of the hip plays an important role in the study of patients with JIA as it reveals early joint involvement and evaluates the extent of joint disease. This permits intervention at an appropriate time with suitable treatment. Clinical and laboratory findings are inadequate diagnostic tools for the assessment of hip arthritis when comparing with MRI.     

Renal amyloidosis: an uncommon complication of juvenile idiopathic arthritis

A 9-year-old girl presented with systemic-onset juvenile idiopathic arthritis, diagnosed at 3.5 of age and which was difficult to control despite several therapeutic trials. Five years after diagnosis of juvenile idiopathic arthritis, nephrotic proteinuria was noticed. Renal biopsy confirmed the diagnosis of amyloidosis, and chlorambucil was initiated, with general improvement of the disease and reduction of proteinuria.     

Clinical characteristics of influenza virus infection in juvenile idiopathic arthritis patients treated with tocilizumab

Background

Inhibition of interleukin-6 (IL-6) signaling by tocilizumab is highly effective for treatment of refractory juvenile idiopathic arthritis (JIA). It appears that IL-6 plays an important role in the immune response to the influenza virus, but it is not clear whether treatment with tocilizumab affects the severity of influenza.

Methods

We retrospectively collected clinical and laboratory data from JIA patients (n = 33) treated with tocilizumab. Ten patients who developed influenza (tocilizumab group; 10.1 %, 10/99 patient-years) were analyzed. Eleven JIA patients who experienced influenza during conventional treatments, without tocilizumab (control group), were compared with the tocilizumab group.

Results

Of the 10 patients in the tocilizumab group, 6 patients did not have high fever (>38 °C), and the other 4 febrile patients recovered from fever in 1 day. White blood cell counts and lymphocyte counts were significantly lower at the acute phase of infection compared with data from before influenza infection. The degree of fever and level of C-reactive protein in the tocilizumab group were significantly reduced compared with the control group.

Conclusions

IL-6 inhibition by tocilizumab reduced inflammation associated with infection and resulted in mild symptoms during influenza. Leukopenia might be a useful indicator of viral infection, including influenza, during tocilizumab treatment.     

Pulmonary function in children with juvenile idiopathic arthritis and effects of methotrexate therapy

Summary Objective To evaluate impairment of lung function as an adverse effect associated with methotrexate therapy in patients with juvenile idiopathic arthritis (JIA). Methods We performed pulmonary function testing including diffusion capacity for carbon monoxide as measured by the single breath method (DLCO-SB) in 89 children with juvenile idiopathic arthritis. Forty (45%) were treated with methotrexate for a median of 24 months (range 3 to 120 months). Except for the presence of asthma in two children, there was no clinical or radiological evidence of pulmonary disease. Results Pulmonary function testing demonstrated moderate airway obstruction in two children with known bronchial asthma. Neither obstructive nor restrictive alteration of ventilation was found in any other patient. Two juvenile idiopathic arthritis patients showed a reduced CO diffusion capacity of 64 and 67%. One of them was treated with methotrexate. Conclusions With regard to lung function impairment treatment with low dose methotrexate appears to be safe even when performed for several years reaching a total amount of up to 3.5 g. In contrast to studies performed in adult rheumatoid arthritis patients, in children with juvenile idiopathic arthritis impairment of lung function is a rare event. Received: 23 February 2001 Accepted: 16 May 2001     

Safety and efficacy of once-weekly application of Etanercept in children with juvenile idiopathic arthritis

Etanercept—a recombinant TNF receptor fusion protein—has been approved for the treatment of resistant polyarticular juvenile idiopathic arthritis. In children with JIA, 0.4 mg/kg is given subcutaneously twice weekly. In adult patients efficacy and safety of etanercept, 25 mg twice weekly was comparable to 50 mg once weekly. In the German paediatric Etanercept registry six patients with JIA were identified, who received Etanercept once weekly primarily and six patients who received Etanercept initially twice weekly and later once weekly with increased dose per injection. In both groups, treatment was efficacious and well tolerated. In patients switching from twice to once weekly administration, there was no loss of efficacy and no increase in toxicity. At last observation 10/12 patients achieved an ACR-JRA 30 and 8/12 achieved an ACR-JRA70 response. These data indicate that once weekly application of etanercept is safe and efficacous in children.     

Tumour necrosis factor alpha promoter polymorphisms and etanercept therapy in juvenile idiopathic arthritis

The objective of this study was to investigate the influence of TNF-α promoter alleles on clinical response to etanercept therapy in JIA. TNF-α promoter polymorphisms at positions −163, −238, −244, −308, −376 were determined in 137 JIA patients treated with etanercept for at least 3 months. A PCR fragment of about 500 bp of the TNF gene promoter was amplified. Polymorphisms were detected by a single sequencing procedure. Patients with the genotype −308GG achieved an ACR-JRA 30 response at month 6 more frequently than patients with the genotype −308GA or AA. This was already notable at month 3 of therapy. This difference in the total patient group is attributable to the JIA subgroup with rheumatoid factor negative polyarthritis. In this subgroup, patients with the −308GG genotype achieved an ACR-JRA 30 response more frequently than those with the −308GA or AA genotype (84 vs. 33% at months three, P < 0.01, 93 vs. 67% at months six, P < 0.05). There was no influence of the −238 TNF-α promoter alleles on clinical response. The rare alleles at position −376 or at positions −163 and −244 were too infrequent. There is an association between TNF gene promoter polymorphisms and response to etanercept in rheumatoid factor negative polyarticular JIA.     

Isolated proximal tibiofibular joint arthritis in a patient with juvenile idiopathic arthritis: A case report

We report the case of a 14-year-old girl of juvenile idiopathic arthritis (JIA) with isolated and chronic proximal tibiofibular (PTF) joint arthritis. The clinical history, magnetic resonance imaging, and pathological findings of the patient are presented. We should be careful to evaluate the patient for chronic lateral knee pain, and consider concomitant evaluation for JIA, including rheumatoid arthritis.