Assessment of Pulmonary Function in Children with Juvenile Idiopathic Arthritis: A Cross-Sectional Study.

To study the serum lipid profile in children with different subtypes of juvenile idiopathic arthritis (JIA) during active and remission stages, as well as the long-term risk of atherosclerosis in children with JIA. A total of 128 children newly diagnosed with active JIA were divided into oligoarticular JIA group with 48 children, polyarticular JIA group with 38 children, systemic JIA group with 22 children, and enthesitis-related JIA group with 20 children. According to the presence or absence of rheumatoid factor (RF), the polyarticular JIA group was further divided into RF-positive polyarticular JIA group with 15 children and RF-negative polyarticular JIA group with 23 children. A total of 45 children who underwent physical examination were randomly selected as healthy control group. The serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured and compared between groups. Blood lipid parameters were reexamined for 87 children in the remission stage after treatment and were compared with those in the active stage. Compared with the healthy control group, the systemic JIA group and the RF-positive polyarticular JIA group had a significant reduction in HDL-C and a significant increase in TG (P<0.05) in the active stage, while there were no significant differences in TC and LDL-C (P>0.05). There were no significant differences in blood lipid parameters between the other subtype JIA groups and the healthy control group (P>0.05). The RF-positive polyarticular JIA group had a significant increase in plasma HDL-C from the active stage to the remission stage (P<0.05), while the other subtype JIA groups had no significant changes in blood lipid parameters (P>0.05). Dyslipidemia may be observed in the active stage of children with systemic and RF-positive polyarticular JIA, with improvement in the remission stage of children with RF-positive polyarticular JIA. Further studies are needed to observe the long-term risk of atherosclerosis.

Juvenile idiopathic arthritis (JIA) is the most common rheumatologic disorder of childhood. It is a group of diseases characterized by chronic synovitis and associated with many extra-articular manifestations including cardiac and pulmonary involvement. Cardiac involvement as pericarditis, myocarditis and valvular disease is common in JIA. There are, however, few descriptions concerning systolic and diastolic functions of the left ventricle (LV) and the development of lung disease in children with JIA. The study was carried out to detect the cardiac and pulmonary involvement and to study the systolic and diastolic function of the left ventricle in a group of children with juvenile idiopathic arthritis. Forty-five children with JIA without any cardiac or pulmonary symptoms and 30 age- and sex-matched controls were included in the study. M-mode, two-dimensional and pulsed Doppler echocardiography (ECHO) was performed on 36 patients. Tissue Doppler ECHO examination was performed on 24 patients to assess systolic and diastolic functions of left ventricle. Pulmonary function tests: Forced vital capacity (FVC%), the predicted forced expiratory volume in the first second (FEV(1)%) and FEV(1)/FVC ratio and peak expiratory flow (PEF), total lung capacity (TLC) and residual volume (RV), carbon monoxide diffusing capacity of the lung (DLCO) and DLCO/alveolar volume (VA) were evaluated in 32 patients. Informed consent was obtained from all children's parents. The study protocol was approved by ethical committee of Faculty of Medicine, Assiut University. In this study, children with JIA had higher systolic and diastolic blood pressures, resting heart rate, left ventricle systolic size and volume (4.35 ± 0.68 vs. 3.92 ± 0.28, P value = 0.02). On Doppler and tissue Doppler analysis, the JIA group had lower peak early filling velocity (E, m/s), higher peak atrial filling velocity (A, m/s) and prolonged diastolic E and A waves deceleration times and isovolumic relaxation time (IRT) compared to control. Regarding pulmonary function tests, children with JIA showed significant decrease in FVC, PEF, Pimax, Pemax and DLCO compared to normal controls. This decrease was not related to age, height or weight of these patients. There was significant inverse correlation between lung function parameters and the rheumatoid factor titer, erythrosedimentation rate, disease duration and the duration of methotrexate use (P < 0.01). Despite of an asymptomatic cardiopulmonary status, significant systolic and diastolic functional abnormalities exist in children with JIA. Also, both restrictive and obstructive lung impairments were found.

Tdap booster to adolescents with juvenile idiopathic arthritis on and off anti-TNF agents is safe and immunogenic

Objectives To determine the frequency of Th2-mediated allergic diseases (AD) in mainly Th1-driven juvenile idiopathic arthritis (JIA) subtypes. Methods Ninety-nine JIA patients and 128 control subjects were enrolled in a prospective case-control study. All subjects were assessed with standard allergy questionnaire, complete blood cell count, and total serum immunoglobulin (sIg) E. sIgs G, A, M, Juvenile Arthritis Disease Activity Score-27 (JADAS27), and serum acute phase reactants (sAPR) were obtained in JIA. In the presence of allergic symptoms, skin prick (SPT) and pulmonary function tests (PFT) were performed. Results Despite similar allergy risk factors, the frequencies of asthma and allergic rhinitis were lower in JIA group (all p ≤ .02). Allergic patients with JIA performed lower FEV1/FVC ratio, PEF, and FEF25–75 compared to the control group (all p ≤ .04). JADAS27 and sAPR were similar among JIA patients with and without AD. Two JIA patients were found to have hypogammaglobulinemia. Conclusion The frequencies of AD, asthma, and allergic rhinitis may decrease in Th1-mediated JIA subtypes although the coexistence does not appear to affect the severity of arthritis whereas allergic symptoms may resolve after immunosuppressive treatment. PFTs should be obtained periodically in JIA. JIA patients may have an underlying primary immunodeficiency (ID) or immunosuppressive drugs may cause secondary ID. KEY POINTS Compared to the population, the frequency of Th2-mediated allergic diseases is lower in oligoarthritis and RF-negative polyarthritis that are primarily driven by a Th1 activity. The coexistence of allergic diseases in juvenile idiopathic arthritis does not affect the severity of arthritis. Pulmonary function tests can be thought to be obtained periodically in juvenile idiopathic arthritis. Immunological workup should be considered in atypically or severely presented patients with juvenile idiopathic arthritis before the initiation of immunosuppressive therapy to differentiate primary and secondary immunodeficiency.

Objective To analyze the relationship between Notch signaling pathway and levels of lymphocytes and cytokines in children with juvenile idiopathic arthritis(JIA), and to explore its role in the pathogenesis of JIA. Methods Thirty-five pediatric patients with JIA [males 20 cases, females 15 cases; aged (6.5±4.0) years old, (0.83-15.00 years old)]and 15 healthy children [males 6 cases, females 9 cases; aged (5.0±2.9) years old, (1.0-11.0 years old)]from November 2015 to February 2016 in Guangzhou Women and Children′s Medical Center were included in the study. The JIA group were divided into the systemonset JIA(So-JIA) group (22 cases) and psoriatic JIA(p-JIA) group (13 cases, polyarthritis 7 cases and oligoarthritis 6 cases). The expressions of Notch signaling′s receptor, ligand and target gene mRNA in peripheral blood monouclear cells (PBMC) from the JIA group and the control group were determined by quantitative real-time PCR.The levels of cytokines interleukin (IL) -1β, IL-10, IL-6, IL-17, IL-4 and transforming growth factor-β (TGF-β) were detected by enzyme-linked immunosorbent assay. Results Compared with the healthy control group, the Notch2 receptors (1.6±3.2 vs. 0.4±0.3) expression level, Jagged1 ligand (44.0±79.0 vs. 11.3±1.2) expression levels and the levels of target gene HES1(0.4±0.3 vs. 0.1±0.1) mRNA in the JIA group showed a significant increase, and the differences were all statistically significant (all P<0.05 ). Compared with the healthy control group, the JIA group showed an increased level of IL-1β [(182.22±309.13) ng/L vs. (54.71±20.33) ng/L], IL-10 [(32.99±34.28) ng/L vs. (22.68±4.56) ng/L], IL-6 [(100.48±305.57) ng/L vs. (13.98±2.78) ng/L], IL-17 [(9.11±17.57) ng/L vs. (2.42±0.29) ng/L] and TGF-β [(14.37±9.33) ng/L vs. (5.49±4.49) ng/L], and there were statistically significant differences (all P<0.05) .The expression level of HES1 mRNA was positively correlated with STAT3 mRNA in the So-JIA group (r=0.573, P<0.05). The expression level of HES1 mRNA was positively correlated with CD3+ T(r=0.528), CD19+B(r=0.480), CD3+ CD4+ TH(r=0.457) and CD16+CD56+NK(r=0.598) cell absolute count in the So-JIA group (all P<0.05). The expression level of HES1 mRNA was positively correlated with CD3+ T cell absolute count in the p-JIA group(r=0.577, P<0.05). Conclusion Imbalance between Notch pathway and lymphocytes and cytokines in children with JIA may play an important role in the pathogenesis of JIA. Key words: Juvenile idiopathic arthritis; Notch pathway; Lymphocytes; Cytokines

Our aim was to compare the periodontal conditions in a group of juvenile idiopathic arthritis (JIA) patients with those in a control group of healthy subjects (CTR). Thirty-two patients with JIA and 24 controls were selected. The measurements used to diagnose periodontal disease included plaque and bleeding scores, probing depths (PDs) and clinical attachment loss (CAL). Laboratory indicators of JIA activity included the erythrocyte sedimentation rate (ESR) and capsule-reactive protein (CRP). The Mann-Whitney test was used to evaluate the data (alpha = 0.05). The mean ages were 15.9 (+/- 2.7) years and 14.7 (+/- 2.3) years for groups JIA and CTR, respectively. The median ESR was 42 mm/h 13 mm/h in the CTR group (p = 0.032) and the median CRP was 1.9 and 0.4 mg/l, respectively (p = 0.001). The prevalence of patients with a proximal attachment loss of 2mm or more in the JIA group was 25% and in controls it was 4.2%. The mean percentages of visible plaque and marginal bleeding were similar in the JIA (54 +/- 22 and 30 +/- 16, respectively) and CTR groups (44 +/- 18 and 29 +/- 11, respectively). The mean percentages of sites with PD > or = 4 mm were significantly higher in the JIA group (3 +/- 4.7) than in the CTR group (0.4 +/- 1.7) (p = 0.012). The mean percentages of sites with proximal CAL > or = 2 mm were 0.7 (+/- 1.4) in the JIA group and 0.001 (+/- 0.2) in the CTR group (p = 0.022). Adolescents with JIA present more periodontal attachment loss than healthy controls, in spite of similar plaque and marginal bleeding levels.

BackgroundThe juvenile (idiopathic) arthritis (JIA) is one of the most common groups of pediatric rheumatic diseases. JIA, as defined by the ILAR, include 7 disease subtypes. Both genetic and environmental...

The pathogenesis of juvenile idiopathic arthritis (JIA) remains unknown, but imbalance between the oxidant and antioxidant defense systems may play a role. Measuring thiols in plasma provides an indirect indication of antioxidative defense. The aim of the present study was to investigate the association between JIA and dynamic thiol/disulfide homeostatic status. This case-control study involved 34 JIA patients and 30 age- and gender-matched healthy controls. Thepatients were divided into subgroups according to Simplified Disease Activity Index (SDAI) score: active, SDAI > 3.3; remission, SDAI ≤ 3.3. Native thiol and total thiol were significantly lower in the JIA group than in the control group (P = 0.001). There was no significant difference in the disulfide/native thiol, disulfide/total thiol, and native thiol/total thiol ratios between the JIA and control groups (P > 0.05). Based on SDAI score, 22 JIA patients were in the remission subgroup, and 12 JIA patients were in the active subgroup. Native thiol and total thiol were significantly lower in the active JIA subgroup than in the remission subgroup (P = 0.001), but there were no significant differences in the other parameters. There was no significant difference in thiol and disulfide levels between systemic-onset JIA and other JIA (P > 0.05). Plasma thiol is lower in JIA patients, especially during periods of active disease, than in healthy controls, indicating that low thiol might be an important factor in the etiology of JIA and that antioxidant systems are negatively affected by inflammatory diseases, especially during periods of active disease.

To evaluate lung function in juvenile idiopathic arthritis (JIA) patients. This was a case control study carried out at Institute of Post-Graduate Medical Education & Research, Kolkata, involving JIA patients between 5 and 12 y. They were diagnosed and classified on the basis of International League of Associations for Rheumatology (ILAR) criteria and compared with same number of age, sex, height and weight matched controls. Forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC ratio, forced expiratory flow between 25 and 75% of vital capacity (FEF25-75%) and peak expiratory flow rate (PEFR) of cases were compared to those of matched controls. Among 36 JIA patients initially recruited, 9 were excluded. Of the remaining 27 patients, male: female ratio was 17:10. Mean age, height and weight of JIA patients were 9.15 y, 124.67 cm and 23.78 kg respectively. Six patients had oligoarthritis, 3 had rheumatoid factor positive (RF+) polyarthritis, 10 had rheumatoid factor negative (RF-) polyarthritis and 8 had systemic JIA. Eleven patients had active disease and 15 patients required methotrexate. None had respiratory symptoms. Mean duration of the disease was 2.96 y. Mean FVC and FEV1 were significantly less in JIA patients compared to controls (p value=0.0003 and 0.0007, respectively). FEV1/FVC in both the groups was similar (p value=0.96). Mean Z scores for FVC and FEV1 were significantly higher in JIA patients (p value=0.0064 and 0.0030, respectively). Spirometry in JIA patients demonstrated statistically significant restrictive pattern of alteration in pulmonary function.

Objectives:The aim of this study was to evaluate the residual value of Conventional Radiography in children with arthralgia clinically suspected of Juvenile Idiopathic Arthritis (JIA).Materials and Methods:Three hundred seventy-two patients aged 1–18 years suspected of JIA were retrospectively reviewed. All patients had foot and ankle plain films performed in standard two projections: ankle in antero-posterior and lateral, and foot in antero-posterior and oblique. The cohort was divided into two groups: patients with confirmed JIA and non-JIA control group of children with foot and ankle arthralgia without diagnosis of inflammatory connective tissue disease. Radiographic findings in both groups were compared.Results:In 40% of JIA and 70% of non-JIA patients radiographs were normal. All radiographic findings were significantly more common in JIA than in non-JIA group (p = 0.000). Soft tissue swelling was the most frequent abnormality found in JIA patients (31, 51%) and only in 2.41% of non-JIA patients (p = 0.000). Osteoporosis and joint space narrowing were also significantly more common in JIA group (p = 0.000). The majority of imaging findings in non-JIA group were non-inflammatory abnormalities.Conclusion:Conventional radiography is an important tool in differential diagnosis of arthralgia of unknown etiology, as soft tissue swelling, osteoporosis and joint space narrowing are significantly more common in JIA patients as compared with patients without the diagnosis of inflammatory connective tissue disease. However, in case of high clinical suspicion of JIA and normal radiography, we recommend subsequent ultrasound (US) and/or MRI to allow early treatment.

Introduction: Juvenile Idiopathic Arthritis (JIA) is a chronic rheumatic disease, with a prevalence of 1 in 1000 children under the age of 16 years. The clinical symptoms include inflammation of joints, swelling of synovial membrane resulting in growth disturbances and loss of bone density. Aim: To assess the effect of JIA on the development of Temporomandibular Joint (TMJ) and occlusion in children and young adolescents in the age group of 8-16 years and to evaluate the effect of TMJ arthritis on the growth of maxilla and mandible. Materials and Methods: This is a descriptive cross-sectional study with a study and control group. A total of 44 children with JIA attending the Department of Rheumatology, Nizam Institute of Medical Sciences (NIMS), within the age group of 8-16 years were screened and enrolled in study from May-July 2014. A gender and sex-matched healthy control group were enrolled from Paediatric Dentistry outpatient specialty. For the measurement and comparison of arch perimeters of mandible and maxilla, the JIA and control group were divided into sub-groups 1 (8-10 y), 2 (11-13 y), and 3 (14-16 y). All the parameters were recorded and subjected to statistical analysis. An Independent sample t-test was used to find a significant difference for maxillary and mandibular arch perimeters among both the groups. Chi-square test was used to know the difference for TMJ parameters, occlusion and occlusal abnormalities. The level of significance was set at p&lt;0.05 for all tests. Results: Children in the JIA group had reported TMJ pain on movement (40.9%), clicking sounds (36.4%), and dislocation (22.7%). Angle’s class II malocclusion was seen in 36.4% compared to the control group (4.5%). The mean arch perimeter of the mandible was significantly less among JIA children in subgroups 2 (73.00±3.03 mm), and 3 (71.77±6.27 mm) when compared to healthy controls. Other occlusal abnormalities such as increased overjet (34.1%), decreased overbite (31.8%), and crowding (54.5%) were reported in significant percentages compared to healthy controls. Conclusion: The mean arch perimeter of the mandible in the JIA group is less when compared to children of the same age in the control group. There is increased predilection of developing Angle’s class II Malocclusion in the JIA group. From a paediatric dentist perspective, it’s important to understand the overall impact of JIA on stomatognathic system, and an early intervention is recommended.

Background:Children with juvenile idiopathic arthritis (JIA) have been found to have reduced cardiorespiratory fitness and lower physical activity. Poor cardiorespiratory fitness is associated with a risk of cardiometabolic diseases.Objectives:The aim of this study was to study the levels of cardiorespiratory fitness, respiratory function and hemodynamic responses during and after maximal cycle ergometer exercise test in children with JIA aged 6-17 years and compare the results with healthy controls.Methods:Study group in this analysis consisted of 43 patients with JIA who were treated in Department of Pediatrics in Kuopio University Hospital, Finland and 40 healthy age- and sex matched controls. Maximal exercise tests were carried out with an electromagnetic cycle ergometer using a pediatric saddle module. Maximal workload per kilogram (Wmax/kg) was used as a measure of cardiorespiratory fitness and was presented relative to bodyweight. In addition the peak values of VO2per kilogram (VO2max/kg) were used as a measure of highest amount of oxygen that an individual can consume during exercise. Values of VO2maxwere collected from respiratory gases measured directly from breath by breath method and was presented relative to body weight.Physical activity and sedentary behavior (minutes per day) was assessed by the PANIC (Physical activity and nutrition in children -study) Physical Activity Questionnaire which the participants filled.Results:Statistical analyses were performed for 43 children with JIA and 40 controls. Mean age in JIA group was 12.09 years (95%Cl 11.04-13.14), and 11.72 years (95%CI 10.52-12.93) in controls (p=0.572). Mean body mass index for age (BMI) was 22.58 kg/m2(95%CI 21.54-23.62) in JIA and 18.95 kg/m2(95%CI 17.73-20.16) in controls (p&lt;0.05). In JIA group BMI was 19.18 % higher compared to controls. Mean physical activity in JIA group was 94.11 minutes per day (95% Cl 81.09-107.13), and 122.54 minutes per day (95% CI 102.84-142.24) in controls, thus JIA group was 23.20 % less physically active than controls (p=0.015).Mean Wmax/kg was 2.65 W/kg (95% CI 2.49-2.82) in JIA and 3.01 W/kg (95%CI 2.86-3.15) in controls thus Wmax/kg in JIA was 0.36 W/kg (11.8 %) lower than in controls, (p = 0.002). VO2max/kg was 37.00 (95%CI 33.96-40.84) ml/kg/min in JIA and 43.30 (95%CI 40.79-45.82) ml/kg/min in controls thus in JIA group mean VO2max/kg was 6.3 ml/kg/min (14.4 %) lower than in controls (p=0.001).Conclusion:Children with JIA were found to have significantly lower cardiorespiratory fitness. In addition, BMI in JIA patients was higher compared to healthy age- and sex-matched controls. Impaired cardiorespiratory fitness and higher BMI may predispose children with JIA to cardiometabolic comorbidities later in life. In addition to disease-control, more attention should be paid to maintaining good cardiorespiratory fitness and normal BMI in these patients already before adulthood.

BACKGROUND: Vitamin D plays essential role in the regulation of inflammation, such as in pathogenesis of Juvenile Idiopathic Arthritis (JIA). Vitamin D deficiency has been reported among JIA patients, but there were conflicting results regarding the correlation with disease activity. This study aimed to assess vitamin D serum level and its correlation with C-Reactive Protein (CRP) and disease activity in JIA patients.METHODS: Children who were diagnosed with JIA according to International League of Associations for Rheumatology (ILAR) criterias were enrolled as JIA group subjects, while age and sex-matched healthy children were enrolled as the control group subjects. Vitamin D and CRP serum level were measured. Disease activity of JIA patients was calculated by Juvenile Arthritis Disease ActivityScore-27 (JADAS-27).RESULTS: Vitamin D serum level was lower in the JIA group compared to the healthy control group (p=0.000). Among 26 JIA patients, 61.5% were deficient, 30.8% were insufficient, and 7.7% had normal vitamin D. No significant different in CRP level between vitamin D group (p=0.441), but there was significant different in JADAS-27 (p=0.001). The mean of CRP and JADAS-27 were found highest in vitamin D deficiency group. Vitamin D serum level was negatively correlate with CRP (p=0.021, r=-0.452) and JADAS-27 (p=0.001 r=-0.595).CONCLUSION: Low level of vitamin D in JIA patients was inversely related to higher CRP and disease activity,suggesting that vitamin D supplementation could be havepotential role in JIA treatment.KEYWORDS: vitamin D, CRP, disease activity,JADAS-27, JIA

BackgroundThere have been inconsistent conclusions regarding salivary abnormalities and their effect on oral health of Juvenile Idiopathic Arthritis (JIA) patients. The purpose of the study was to evaluate the flow rate and selected biochemical parameters of unstimulated whole saliva in correlation to oral health in JIA children.MethodsThirty-four JIA patients and 34 age- and sex-matched controls not affected by JIA (C) were divided into two groups: with mixed and permanent dentition. DMFT/dmft, gingival and simplified oral hygiene indices were evaluated. Salivary flow rate, pH, lysozyme, lactoferrin, salivary protein concentrations and peroxidase activity were assessed.ResultsThe salivary flow rate was significantly lower in the total JIA group (0.41 ml/min) as compared with the C (0.51 ml/min) and in the permanent dentition of JIA children (0.43 ml/min) as compared with the C (0.61 ml/min). A significantly lower pH was observed in total (6.74), mixed (6.7) and permanent (6.76) dentition of JIA groups in comparison to the C (7.25, 7.21, 7.28 respectively). The specific activity of peroxidase was significantly higher in JIA patients (total 112.72 IU/l, mixed dentition 112.98 IU/l, permanent dentition 112.5 IU/l) than in the C group (total 70.03 IU/l, mixed dentition 71.83 IU/l, permanent dentition 68.61 IU/l). The lysozyme concentration in JIA patients (total and permanent dentition groups) was significantly higher than in the C group. There were no significant differences in lactoferrin and salivary protein concentrations. There were no statistically significant differences in oral status between JIA patients and C, respectively: DMFT = 5.71, dmft = 3.73, OHI-S = 0.95, GI = 0.25 and DMFT 5.71, dmft = 3.73, OHI-S = 0.85, GI = 0.24. The specific activity of peroxidase in the unstimulated whole saliva was inversely correlated with the GI index, whereas the salivary lysozyme concentration was inversely correlated with the dmft index in JIA patients.ConclusionIn the course of JIA occur a reduction of the resting salivary flow rate and a decrease of saliva pH. In spite of this, no differences in the clinical oral status between the JIA children population and the control group were found. The mobilisation of salivary peroxidase and lysozyme contributes to the maintenance of healthy oral tissues.

The pathogenesis of juvenile idiopathic arthritis (JIA) is strongly influenced by an impaired immune system. However, the molecular mechanisms underlying its development and progression have not been elucidated. In this study, the computational methods TRUST4 were used to construct a T-cell receptor (TCR) and B-cell receptor (BCR) repertoire from the peripheral blood of JIA patients via bulk RNA-seq data, after which the clonality and diversity of the immune repertoire were analyzed. Our findings revealed significant differences in the frequency of clonotypes between the JIA and healthy control groups in terms of the TCR and BCR repertoires. This work identified specific V genes and J genes in TCRs and BCRs that could be used to expand our understanding of JIA. After single-cell RNA analysis, the relative percentages of CD14 monocytes were significantly greater in the JIA group. Cell-cell communication analysis revealed the significant role of the MIF signaling pathway in JIA. In conclusion, this work describes the immune features of both the TCR and BCR repertoires under JIA conditions and provides novel insight into immunotherapy for JIA.