Modifications of the Effect of Juvenile Idiopathic Arthritis (JIA) on Anxiety and Depression in Children and Adolescents: A Pseudo-longitudinal Study of 192,019 Children in the United States

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.

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.

The assessment of long-term outcome of functional disability and disease activeness in adult patients with juvenile idiopathic arthritis appears to be complicated due to the absence of a unified approach to the classification and estimation of disease activeness, as well as the loss of supervision over a patient because of remission or his/her transition from pediatric to adult rheumatic service. The objective of the research was to determine how adults with the history of juvenile idiopathic arthritis fulfill the classification criteria for adult rheumatic diseases, as well as to assess activeness of these diseases, the degree of functional disorders, and social activeness of patients in Ukraine. Materials and methods. Patients with juvenile idiopathic arthritis older than 18 years and with more than 3 years of disease duration living in different parts of Ukraine were included into the study. Data regarding sociodemographic features, fulfillment of adult classification criteria, Health Assessment Questionnaire, articular and extra-articular Juvenile Arthritis Damage Index and disease activity were analyzed.Results. We observed 122 adult patients with the history of juvenile idiopathic arthritis irrespective of the presence of active inflammation at the moment of the examination. This group included patients from different regions of Ukraine diagnosed with juvenile idiopathic arthritis during 1984-2013. An adult rheumatologist examined all patients and the diagnosis was revised according to the adult classification of rheumatic diseases. Typical diagnostic criteria for rheumatoid arthritis were estimated in 32.8% of patients, ankylosing spondylitis – in 31.1% of patients, undifferentiated arthritis – in 13.9% of patients, Still’s disease – in 4.9% of patients, psoriatic arthritis – in 0.8% of patients, steady clinical laboratory remission – in 16.5% of patients. Most patients (81.8%) with rheumatoid factor positive polyarticular juvenile idiopathic arthritis fell under rheumatoid arthritis criteria in adulthood, and in 85% of patients with enthesitis-related arthritis as well as 53.8% of patients with extended oligoarthritis ankylosing spondylitis developed in adulthood. 68.8% of patients with systemic juvenile idiopathic arthritis, 68% of patients with rheumatoid factor negative polyarthritic subtype and 55% of patients with enthesitis-related arthritis had disability and incapacitation. Minimal disorders of the patients’ general condition according to the Health Assessment Questionnaire in adult age were found in most subtypes of juvenile idiopathic arthritis classified according to the International League of Associations for Rheumatology (extended and persistent oligoarthritis, rheumatoid factor positive polyarthritis, systemic subtype); moderate disorders of the general condition were found in enthesitis-related arthritis and rheumatoid factor negative polyarthritis. Side effects of juvenile idiopathic arthritis according to the articular Juvenile Arthritis Damage Index included severe articular damage being most frequently found in systemic and rheumatoid factor positive polyarthritis subtypes of juvenile idiopathic arthritis, while side effects of juvenile idiopathic arthritis according to the extra-articular Juvenile Arthritis Damage Index included extra-articular damage being found in systemic and rheumatoid factor negative polyarthritis subtypes of juvenile idiopathic arthritis, that was confirmed by the assessment of physical health according to the Short Form Health Survey-36, which was the worst in patients with systemic (40.3±12.6) and rheumatoid factor negative polyarthritis (38.9±9.4) subtypes of juvenile idiopathic arthritis.Conclusions. Further research of remote consequences of juvenile idiopathic arthritis in adult age and long-term observation of such patients require a detailed study to improve diagnostics and provide adequate treatment of rheumatic diseases with juvenile onset in adult age.

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...

Juvenile idiopathic arthritis (JIA) is a chronic autoimmune disorder characterized by joint inflammation, potentially leading to pulmonary involvement. This study aimed to assess pulmonary function in children with JIA compared to controls and identify potential respiratory abnormalities associated with the disease. This was a prospective cross-sectional study conducted at the Pediatric Rheumatology, Başakşehir Çam and Sakura City Hospital, İstanbul, Türkiye, between July and October 2024. The study included 70 children with JIA and 60 healthy controls aged 6 to 17. Pulmonary function test parameters, such as forced vital capacity (FVC), forced expiratory volume in the 1st second (FEV1), peak expiratory flow (PEF), and FEV1/FVC ratio, were measured using spirometry. Oxygen saturation (SpO2) was also measured. There were no significant differences in demographic and clinical characteristics between the JIA and control groups (p > 0.05). FVC and FEV1 values were lower in the JIA group, though not significantly (p = 0.831 and p = 0.711). However, PEF was significantly lower in the JIA group than controls (p = 0.005). Children with moderate or high disease activity had significantly lower FVC, FEV1, and FEF 25-75 than those with low disease activity (p < 0.001). Enthesitis-related arthritis patients had higher FVC and FEV1 than other JIA subtypes (p < 0.05). FVC and FEV1 were positively correlated with BMI (p < 0.001). Although PEF values were significantly lower in children with JIA, overall pulmonary function was comparable between the groups. Regular pulmonary monitoring in JIA patients is recommended for early detection and management of respiratory complications.

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

BackgroundA decrease in bone mass has been described in a high percentage with increased risk of osteoporosis in JIA subtypes. The pathogenesis of bone loss in active JIA is complex,...

Background The etiology of Juvenile Idiopathic Arthritis (JIA) remains unknown, despite a range of proposed mechanisms under investigation [1]. However, previous research has revealed biological differences depending on the age of onset of JIA, independent of the classification based on the number of joints involved [2]. Objectives In this parent-led study, the age of onset of JIA by both disease subtype and sex of the child were explored, to identify whether there is a difference in age of onset of JIA between males and females. Methods An online survey was shared via social media, targeted at parents of children and young people (CYP) with JIA. Questions probed the age of symptom-onset and diagnosis (by single year of age), JIA subtype and Rheumatoid Factor (RF) status. Results Of the 409 CYP included, 296 had polyarticular (poly) or oligoarticular (oligo) JIA, including extended-oligo JIA (72% of all respondents). There were no differences between onset among these subtypes; therefore, they were grouped for further analysis, given comparable disease progression and genetic markers among these subtypes. There was no significant difference regarding age of symptom onset between RF-positive and RF-negative CYP. Amongst those with poly/oligo JIA, there was a clear peak of symptom-onset in the first few years of life, with over half experiencing symptoms before their third birthday, and 73% before the age of five years. Interestingly, the distribution of symptom-onset was significantly different in the poly/oligo JIA group between males and females (P=0.0093), with the onset of poly/oligo JIA appearing to occur earlier in females (Figure 1). Given that some CYP with older-onset JIA are sometimes reclassified as having enthesitis-related arthritis (ERA) when examined in adolescent services, the Mann-Whitney U Test was repeated with only those CYP with JIA onset before the age of seven years. In this case, there remained a significant difference in age of onset of poly/oligo JIA between males and females (P=0.0061). Conclusion The age of symptom-onset among CYP with poly/oligo JIA differs between males and females, with females tending to exhibit symptoms earlier. This appears not to be attributable to misclassification of JIA subtype, and so this knowledge may assist future diagnoses of JIA. Further research is required to identify which temporal-associated factors may be critical in JIA onset and development.

BackgroundWhole-body MRI (WBMRI) enables a comprehensive assessment of joint inflammation in children and young people (CYP) with juvenile idiopathic arthritis (JIA). The clinical relevance of WBMRI-detected inflammation in joints requires...

Objectives: The aim of this study was to assess the effect of juvenile idiopathic arthritis (JIA), its subtypes and disease activity on anthropometric measurements, body composition, and nutritional parameters.Method: A cross-sectional cohort of 40 JIA patients, aged 3–10 years, was compared with 40 healthy children matched for age and gender. Concentrations of nutritional and inflammatory biomarkers in the blood, anthropometric measures, and clinical status were recorded and the parents filled in a 7-day food diary and completed the Childhood Health Assessment Questionnaire (CHAQ).Results: The JIA patients had low disease activity: 60% had inactive disease, the median CHAQ score was 0.125, and the median erythrocyte sedimentation rate (ESR) was 6 mm/h. Significantly higher values for central and peripheral adiposity were found in JIA patients compared with in healthy controls [waist circumference mean (SD) 55.9 (4.9) vs. 53.4 (3.7) cm, p < 0.0001, and biceps skinfold thickness 6.2 (2.3) vs. 5.3 (1.7) cm, p = 0.035, respectively], and obesity/overweight was more common (30% vs. 12.5%, p = 0.056, respectively) despite no differences in weight-for-height. The intake of energy (kcal/day) was significantly higher in the JIA patients (p = 0.036). The nutritional biomarkers were comparable in both groups. The JIA subtype and disease activity did not affect body composition, energy intake, or the nutritional biomarkers.Conclusions: Even JIA patients with low disease activity have a higher central and peripheral adiposity and a higher energy intake than their healthy peers. Neither disease subtype nor disease activity had any association with changes in body composition.

Background Biologic disease-modifying antirheumatic drugs (DMARDs) are frequently used in the treatment of juvenile idiopathic arthritis (JIA) resistant to nonbiologic DMARDs recently. There is a concern for their reducing the effectiveness of vaccines due to immunosuppresive effects. Objectives To evaluate hepatitis B antibody (anti-HBs) positivity and antibody titers between JIA patients on biologic DMARDs therapy and healthy conrols. Methods Anti-HBs antibody positivity and titers were compared between 88 patients with JIA on biologic DMARDs therapy followed in our clinic and 91 healthy controls aged 2-19 years. All participants were vaccinated according to the routine vaccination schedule in our country. Results Eighty-eight JIA patients included and fifty five (62,5%) patients were female. The median age of patients was 13,31 (4,07-18,08) years. The JIA subtypes were systemic JIA (10,2%), oligoarticular JIA (33%), poliarticular JIA (25%), entesitis related arthritis (26,1%), psoriatic JIA (3,4%), and undifferantiated JIA (2,3%). The median duration of biologic DMARDs was 31,995 (1,33-115) months. 54 patients were treated only with one anti-TNF (34 etanercept, 17 adalimumab), 16 patients were treated more than one TNF-alfa inhibitor. 18 patients were treated with more than one different group biologic DMARDs, and 7 of them had more than two biologic DMARD due to disease activity. Anti-HBs positivity was 67% in the JIA group and 54,9% in the control group, and no significant difference detected between the two groups (p=0,097). The anti-HBs titer was 12,95 (min-max: 2-1000) in the controls and 22,44 (2-1000) in the biological DMARDs. Conclusion Patients with JIA on biologic DMARDs had not lower anti-HBs positivity than healthy controls in our study. Further studies are required to understand the effects of biologic DMARDs on protective anti-HBs antibody levels. Disclosure of Interests None declared

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.

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.

Background/Objectives: The pathophysiology of juvenile idiopathic arthritis (JIA), the most widespread rheumatologically illness in juvenile period, is shaped by complex interactions between leukocytes and the cytokines they secrete. The aim of this research was to evaluate the severity of sleep disturbances and depression, which are closely associated with many diseases and can negatively impact the course of the illness, in patients with JIA using Beck Depression Inventory (BDI) and Sleep Disturbance Scale for Children (SDSC) scores and to investigate the relationship between these scores and laboratory findings in patients with JIA. Methods: The research involved 58 children with JIA and 71 healthy children as controls. BDI and SDSC scores of these groups were compared with laboratory findings and correlation analysis were performed. Results: In the JIA group, BDI and SDSC scores, C-reactive protein (CRP), red blood cell distribution width (RDW), erythrocyte sedimentation rate, neutrophil, and leukocyte counts, were higher than in the control group, while vitamin D values were lower. A positive relation was determined between BDI and SDSC scores in the JIA group, but no correlation was found in the control group. In the JIA group, both BDI and SDSC scores were found to be negatively related with leukocyte and neutrophil counts. In the control group, the BDI score was determined to be negatively correlated with CRP, vitamin D and RDW levels. Conclusions: Depression and sleep disorders may interact in patients with JIA, and their causal relationship with leukocyte and neutrophil levels should be investigated.

Juvenile idiopathic arthritis (JIA) has three major onset types with widely varying clinical features: systemic, polyarticular and pauciarticular. We assessed natural killer (NK) cell function and killer cell immunoglobulin-like receptor (KIR) genotypes in patients with different JIA subtypes. Peripheral blood samples from 72 children with active JIA (systemic, 25; polyarticular, 24; pauciarticular, 23) and 25 controls were used for flow cytometric assessments of NK cell count, cytotoxicity, perforin, granzyme B, interferon (IFN)-γ and tumour necrosis factor (TNF)-α. Samples from 220 children with JIA (systemic, 84; polyarticular, 72; pauciarticular, 64) and 150 controls were used for KIR2DS2, KIR2DS4, KIR3DS1, KIR2DL1, KIR2DL2, KIR2DL3 and KIR3DL1 typing by polymerase chain reaction with sequence-specific oligonucleotide probes. Compared with the controls, the patients with systemic JIA showed lower NK cell counts, cytotoxicity and perforin and granzyme B expression (p<0.05), while the patients with pauci- and polyarticular JIA showed higher perforin and granzyme B expression (p<0.05). NK cells produced higher level of TNF-α while lower level of IFN-γ in the pauci- and polyarticular JIA groups than in the systemic JIA group (p<0.05). No significant differences in KIR gene frequencies were found between the JIA subgroups and healthy controls, except for the positive frequency and locus frequency of KIR2DS4, which were lower in the systemic JIA group. Compared with poly- and pauciarticular JIA, systemic JIA is associated with decreased NK cell function, more IFN-γ and less TNF-α secretion of NK cell and lower KIR2DS4 frequency.