Juvenile Idiopathic Arthritis Duration Research Articles

RISK FACTORS AND CLINICAL CORRELATIONS OF URINARY TGF-Β1 IN CHILDREN WITH JUVENILE IDIOPATHIC ARTHRITIS AND EARLY KIDNEY FIBROSIS

The course of juvenile idiopathic arthritis (JIA) is associated with a long-term infl ammatory process and the use of nonsteroidal anti-infl ammatory drugs (NSAIDs), which can cause nephrotoxicity with fi brotic kidney damage in patients with JIA. Regardless of the etiology of joint damage, prolonged infl ammation promotes the progression of fi brosis, and renal fi brosis is the fi nal common stage of chronic kidney disease (CKD). Kidney biopsy, which is invasive, risky and underutilized, is generally considered the only clinical method to detect fi brosis. Over the past decade, some progress has been made in the search for minimally invasive biomarkers of early kidney fi brosis, with transforming growth factor-β1 (TGF-β1) playing a key role in the progression of kidney fi brosis, but the signifi cance of TGF-β1 in children with JIA is unknown.Material and Methods: 80 children with JIA were examined. Urinary TGF-β1 levels were determined using a TGF-β1 ELISA kit(DRG International, Inc., Germany, EIA-1864) according to the manufacturer’s instructions. Methods of variation statistics were used. Informed consent was obtained from all patients. The study has a positive conclusion of the Commission on Biomedical Ethics of Dnipro State Medical University (Minutes of the meeting of the Commission No. 12 dated December 19, 2002), which decided that the scientifi c research can be considered in accordance with generally accepted moral standards, the requirements of respecting the rights, interests and personal dignity of study participants, bioethical standards for work with pediatric patients. There is no risk to the research subjects in the performance of the work. The legal representatives of the children involved in the research are informed about all aspects related to the purpose, objectives, methods and expected benefi ts of the research. Laboratory and instrumental research methods are generally accepted; the drugs to be used are approved for use. No human experiments were performed.Methods of variation statistics were used. Statistical analysis was performed using the STATISTICA 6.1 software package(StatSoft Inc., serial no. AGAR909E415822FA). The work was carried out as part of the research work of the Department of Propaedeutic of Childhood Diseases and Pediatrics 2 of the Dnipro State Medical University «Development of criteria for early diagnosis and prediction of comorbid kidney damage in children with somatic and infectious diseases» (state registration No. 0119U100932, implementation period 01.2019-12.2023).Results. The mean TGF-β1 level in our study was 20.26±16.34 (14.02, 12.5-17.98) pg/ml. Polyarthritis almost quadrupledthe probability of pathological changes in TGF-β1. The overwhelming majority of children with elevated TGF-β1 suff ered from polyarthritis (80.0 %) – one and a half times more often than those with relatively normal TGF-β1 concentration, p<0.04.If the active stage of the disease lasted at least 4 years, the probability of elevated TGF-β1 increased more than sixfold. Thetendency of signifi cant nephrotoxic eff ect of prolonged active JIA was confi rmed by the results of correlation analysis, according to which, in general, the duration of active JIA was directly related to the increase of TGF-β1 (ρ=0.38, p<0.001), and the duration of remission and the total duration of JIA had no signifi cant correlation with it (ρ= –0.19 and ρ=0.18, respectively, p>0.05). The direct dependence of elevated urinary TGF-β1 levels on clinical features such as polyarthritis and the duration of the active phase of JIA has been demonstrated. These clinical features in children with JIA can be considered as risk factors for the development of early renal fi brosis. Against the background of elevated TGF-β1, a reduced GFR according to the Hoek formula (<90 ml/min/1.73 m2) was found in 95 % of cases, i. e. the estimates of the functional state of the kidneys obtained by two diff erent methods were quite clearly the same. In the sample with TGF-β1<17.98 pg/ml, 22.76 % of children received immunobiologic therapy, while in the sample to increase TGF-β1 – only 14.76 %. Immunobiological therapy reduced the risk of increasing this urinary marker by 5.5 times.Conclusions. Elevated levels of the TGF-β1 biomarker were found in 25 % of children with JIA. An association of early renalfi brosis with duration of active phase of JIA ≥ 4 years, increased ESR, polyarthritis, arterial hypertension, and dental carieswas observed. Elevated urinary TGF-β1 levels are associated with reduced eGFR and are observed in almost all children witheGFR<90 ml/min/1.73 m2, confi rming the importance of early renal fi brosis in the development of renal dysfunction.

How common is remission in rheumatoid factor-positive juvenile idiopathic arthritis patients? The multicenter Pediatric Rheumatology Academy (PeRA) research group experience

ObjectiveRheumatoid factor (RF)-positive polyarthritis is the least common type of juvenile idiopathic arthritis (JIA). Functional disability in RF-positive polyarthritis patients is much more severe than in patients with other subtypes; but data on this subtype alone is limited. This study aimed to analyze clinical features, long-term follow-up, treatment response, and remission status in a large multicenter cohort of RF-positive polyarthritis patients.MethodsThis retrospective study included RF-positive polyarthritis patients that were followed up for ≥ 6 months between 2017 and 2022 by the Pediatric Rheumatology Academy (PeRA)-Research Group (RG). Data on patient demographics, clinical and laboratory characteristics were obtained from medical charts. JIA treatments and duration of treatment were also recorded. The patients were divided into 2 groups based on methotrexate (MTX) response, as follows: group 1: MTX responsive, group 2: MTX unresponsive. Clinical and laboratory findings were compared between the 2 groups.ResultsThe study included 56 (45 female and 11 male) patients. The median age at onset of RF-positive polyarthritis was 13.2 years [(interquartile range) (IQR): 9.0–15.0 years] and the median duration of follow-up was 41.5 months (IQR: 19.5–75.7 months). Symmetrical arthritis affecting the metacarpophalangeal and proximal interphalangeal joints of the hands was commonly observed. Subcutaneous MTX was the preferred initial treatment; however, it was ineffective in 39 (69.6%) of the patients. Of 25 patients followed for 24 months, 56% still had active disease at 24 months.ConclusionDuring 2 years of treatment, 44% of RF-positive polyarthritis patients have inactive disease, and they should be considered as a distinct and important clinical entity requiring aggressive and early treatment.

Different types of juvenile idiopathic arthritis in children presenting in a tertiary care hospital.

Objective: To determine the frequency of different types of juvenile idiopathic arthritis (JIA) in children presenting in a tertiary care hospital. Study Design: Cross-sectional study. Setting: Department of Pediatrics, Children Hospital Complex & Institute of Child Health Multan. Period: January 2021 to July 2021. Material & Methods: Children of both genders with diagnosis of JIA aged 6-12 years and having duration of illness more than six weeks. Age, gender and duration of JIA were noted. Stratification of confounder variables e.g., age, gender and duration of JIA was done. Post-stratification Chi-square test was applied to determine the effect of the variables on frequency of different forms of arthritis. P-value <0.05 was taken as significant. Results: In a total of 121 children, mean age was 8.84±1.83 years. 72 (59.5%) were boys. Mean duration of symptoms was 7.93±4.61 months. Oligoarticular JIA was most common type diagnosed in 40 (33.1%) children followed by polyarticular JIA in 37 (30.6%). Oligoarticular and polyarticular JIA were significantly more common in boys (67.5% and 67.6%) compared to girls (32.5% and 32.4%) respectively (p<0.001). Conclusion: Oligoarticular JIA sub-type is the most common subtype of JIA. Identification of these different subtypes is beneficial for diagnosis and long-term treatment of such children.

Juvenile idiopathic arthritis-associated uveitis: the experience in Libya

Background: Juvenile idiopathic arthritis (JIA) is the most common childhood rheumatic disease. The development of associated uveitis represents a significant risk for serious complications, including permanent loss of vision. Initiation of early treatment is important for controlling JIA-uveitis, but the disease can appear asymptomatically, making frequent screening procedures necessary for patients at risk. As our understanding of pathogenic drivers is currently incomplete, it is difficult to assess which JIA patients are at risk of developing uveitis. In the present study, we described the prevalence and clinical profile of JIA-associated uveitis and out come among children in the Libyan clinical settings. Methods: A total of 90 JIA patients who fulfilled International League of Associations for Rheumatology (ILAR) diagnostic criteria were included in this retrospective study. The data collected were age, gender, age at disease onset and at diagnosis, and follow-up duration. Duration from JIA diagnosis to uveitis diagnosis. Antinuclear antibody (ANA), rheumatoid factor (RF), and human leukocyte antigen B-27 were evaluated for each patient. Results: A total of eight uveitis cases were identified among the 90 JIA cases, which gives a prevalence of 8.9%. All cases were females (100.0%), the majority were Libyans (87.5%), and their mean age was 12.3 (SD=4.3) years old. The mean age at JIA onset for this group was 5.3(SD=2.3) years old and that for JIA diagnosis 6.2 (SD=2.6) years old, with an average duration of JIA of 6.8 (SD=3.7) years. The most common JIA subtype in this group was oligoarthritis (50%), followed by poly arthritis (37.5%). The majority of the cases had a negative rheumatoid factor test (75%), and ANA was positive only in 1 of 7 valid cases (14.3%). Conclusion: Better recognition of uveitis in JIA is required to improve its outcome and avoid serious complications.

Assessment of bone mineral density and bone turnover markers in patients with juvenile idiopathic arthritisy

Juvenile idiopathic arthritis (JIA) is one of the most common chronic inflammatory diseases occurring in childhood, associated with decreased bone mineral density (BMD) and increased risk of osteopenia and osteoporosis, which increases the fracture risk. Aim of the work: to assess BMD and bone turnover markers (serum osteocalcin for bone formation and C terminal telopeptide of type 1 collagen for bone resorption) in JIA patients and their relation to disease activity. This study included 50 patients with JIA (female:male – 20:30). The study was approved by the Ethical Research Committee and Institutional Review Board of the Faculty of Medicine, Menoufia University, Egypt (Approval number: 19519INTPH48). Written informed consent was obtained from each patient or the parents. These patients were diagnosed with JIA according to the criteria of classification of the International League of Associations for Rheumatology. BMD was measured by Dual-energy X-ray absorptiometry (DEXA) of the lumbar spine using the Z-score. The results were correlated with JIA disease duration, disease activity, bone turnover markers and serum level of vitamin D. Clinical disease activity was evaluated by juvenile arthritis disease activity score (JADAS-27). There was a significant negative correlation between DEXA Z-score and disease activity (p-value < 0.001), bone turnover markers (p-value < 0.001), and duration of JIA (p-value < 0.05). There was a significant difference between vitamin D level and DEXA Z-score; DEXA Z-score was lower in vitamin D deficient patients. JIA patients with higher disease activity are at a higher risk of osteopenia and osteoporosis. Well-timed and efficient treatment of JIA and proper control of disease activity may help to improve the bone status and reduce the incidence of osteoporosis. Consequently, valuable targeted interventions are essential to preserve bone health during JIA.

A Nordic screening guideline for juvenile idiopathic arthritis-related uveitis.

The purpose of this perspective was to shed light on screening of uveitis among Nordic children with juvenile idiopathic arthritis (JIA). A literature search was conducted to review predictors of JIA-uveitis and previous JIA-uveitis screening recommendations. Predictors of uveitis in JIA are younger age and positive antinuclear antibody titre at onset of JIA, specific subtypes of JIA (extended and persistent oligoarthritis, rheumatoid factor negative polyarthritis and psoriatic arthritis) and short duration of JIA. Methotrexate and monoclonal tumour necrosis factor (TNF) inhibitor treatment reduce the risk JIA-uveitis. Children with all of the above risk factors should be screened frequently but if they receive TNF inhibitor or methotrexate therapy, they may be screened less frequently. Children with none of the risk factors do not benefit from long-term screening for uveitis. A guideline for intervals and overall length of screening was prepared considering currently known risk factors for JIA-uveitis, the Nordic population and previous guidelines.

Content of natriuretic peptide (NT-proBNP) in patients with juvenile idiopathic arthritis

ABSTRACT. As a result of a cascade of immune-inflammatory reactions, the development of a chronic inflammatory process, systemic damage to the endothelium of vessels in rheumatic diseases, and in particular arthritis, are pathological conditions that are associated with the formation of a number of comorbid changes in internal organs and systems. The most significant are changes in the functioning of the cardiovascular system, with the gradual development of chronic heart failure. An informative marker of myocardial dysfunction is an increase in the level of natriuretic peptide (NT-proBNP). Purpose. Determination of the content of NT-proBNP in children with juvenile idiopathic arthritis, taking into account the functional state of the myocardium. Materials and methods. 56 patients with juvenile idiopathic arthritis were examined (polyarthritis - 86%; oligoarthritis - 14%, 17 boys, 39 girls). The average age is 13.28 ± 0.38 years. The duration of juvenile idiopathic arthritis was from 12 to 180 months (68.96 ± 6.29 months). The control group consisted of 46 (27 boys and 19 girls) practically healthy peers of the corresponding age (14.72 ± 0.28 years). The functional state of the heart was determined, namely the parameters of the left and right ventricles: ejection fraction, stroke volume and minute blood volume. The study of NT-proBNP in the blood was carried out by the method of competitive immunoassay on the IMMULITE 2000 Siemens analyzer. The results. The study of the content of NT-proBNP in children with juvenile idiopathic arthritis showed its normal levels (41.12 ± 6.86 pg/l), but in the control group they were significantly lower than in sick children (29.27 ± 5.23 pg/l , p < 0.01). No differences were found in the level of NT-proBNP depending on the gender of the patients, the variant of juvenile idiopathic arthritis and the degree of its activity. Indicators were significantly higher in children 11-14 years old (49.04 ± 10.22 pg/l, p < 0.05) and with disease duration up to five years (57.04 ± 12.37 pg/l, p < 0.05). The study of the functional state of the myocardium in sick children determined a tendency to decrease the contractile function of the myocardium of both the left and right ventricles of the heart against the background of a decrease in the stroke volume of both ventricles, as well as an acceleration of the heart rate. The mean level of NT-proBNP was significantly higher in the group of children with lower left (pt < 0.01) and right ventricles ejection fraction (pM-U < 0.01). Conclusions. The content of NT-proBNP in patients with juvenile idiopathic arthritis remains within normal values, but is significantly higher than in healthy peers (p < 0.01). The highest values of NT-proBNP in patients with juvenile idiopathic arthritis were among adolescents aged 11-14 years (p < 0.05), as well as with disease duration up to five years (p < 0.05). A decrease in the functional state of the myocardium of both ventricles of the heart in patients with juvenile idiopathic arthritis is accompanied by an increase in the content of NT-proBNP, which is the basis for additional examination of the functional state of the heart already in adolescence for the purpose of early prevention of complications.

24 Scoliosis in children with juvenile idiopathic arthritis: any link?

BackgroundJuvenile idiopathic arthritis (JIA) is an unusual aetiology of scoliosis in childhood. With few data in literature, the associated factors of scoliosis in JIA are still unknown.ObjectivesTo describe the incidence and associated factors of scoliosis in children with JIA.MethodsA cross-sectional study including children with JIA according to the International League of Associations for Rheumatology (ILAR). The recorded data included anthropometric measurements (weight, size, body mass index (BMI), and leg length), disease characteristics (JIA subtypes and duration), and static foot posture disorders. Regarding scoliosis, we collected clinical and radiographic findings.ResultsThirty-five patients, forty-three percent of the patients were boys (n = 15). The mean age was 12.2 ± 3.61 years. The mean disease duration was 4.1 ± 3.29 years. The mean patient global assessment and the mean visual analogic scale were 3.4 ± 3.02 and 3.37 ± 2.92, respectively. The patient's distribution of JIA subtypes was oligoarticular (n = 13), enthesitis-related arthritis (n = 9), polyarticular (n = 4), undifferentiated (n = 4), psoriasis-related JIA (n = 4) and systemic-onset (n = 1). The mean CRP and ESR were 7.51 ± 11.85 mg/l and 18.88 ± 15.53 mm, respectively. The mean JADAS was 7.58 ± 6.3. Seventeen percent of the patients had an inactive disease (n = 6). Seven patients (20%) (6 females) had developed scoliosis during their disease, the spine regions of scoliosis were thoracolumbar scoliosis (n = 6) and thoracic scoliosis (n = 1). There was no specific distribution of scoliosis among JIA subtypes (p = 0.464). Most patients with scoliosis had associated leg length discrepancy (71.43% vs 28.57%, p = 0.025). Static foot posture disorders were present in most patients with scoliosis (85.71% vs 14.29%) but this difference was not significant (p = 0.673) compared with patients with no scoliosis. Weight, size and BMI were not associated with scoliosis (p = 0.955, p = 0.922, p = 0.303 respectively).ConclusionOur study shows that scoliosis is associated with leg length discrepancy. Indeed, the joint inflammation of the lower limb may explain the postural syndrome in children with JIA, with a prompt impact on the axial skeleton.

Эффективность и безопасность отмены ингибиторов фактора некроза опухоли альфа при длительной ремиссии ювенильного идиопатического артрита без системных проявлений: когортное исследование

The biological agents when long-term clinical remission of juvenile idiopathic arthritis (JIA) is achieved is necessary to reduce the risk of side effects and costs and to minimize the non-economic burden of therapy on patients and their families. Objective. To evaluate the efficacy and safety of discontinuing inhibitors of tumor necrosis factor alpha (TNF-α) in patients with JIA without systemic manifestations due to long-term clinical remission. Patients and methods. A total of 137 patients with JIA (27.0% male, mean age: 10 years) were enrolled in this study, of whom 95 (69.3%) received etanercept (0.8 mg/kg/week) and the rest – adalimumab (24 mg/m2 once every two weeks). The retrospective study included patients with JIA without systemic manifestations and disease remission of ≥24 months, during which the patients received TNF-α inhibitors. The latter were discontinued as directed by a physician or due to unavailability of the drug. The primary outcome measure of the study was maintenance of clinically inactive disease status (according to American College of Rheumatology criteria) for 6 months (<210 days including 30 days’ tolerance for deviation from the recommended rehospitalization time) after discontinuation of therapy with TNF-α inhibitors. Results. At the time of TNF-α withdrawal, the median duration of JIA was about 6 years, the duration of TNF-α therapy was 3.5 years, and remission lasted for 3 years. After TNF-α withdrawal, 60 (43.8%) patients continued therapy with traditional disease-modifying antirheumatic drugs (DMARs). In the first 210 days after TNF-α discontinuation, 92 (67.2%) patients with JIA maintained the inactive disease status. The median time for the development of JIA exacerbations in 45 patients was 123 (95; 150) days. Biological agents therapy was resumed in 42 of 45 patients, and the inactive disease status was achieved in 41 cases. DMARs were received by 23 (55%) of 42 patients on therapy with biological agents. Conclusion. In two thirds of patients with JIA, the discontinuation of TNF-α inhibitors due to long-term clinical remission did not lead to disease exacerbations in the next six months. The resumption of biological agents therapy in case of JIA worsening allows most patients to reach the status of clinically inactive disease. Key words: genetically engineered biopharmaceutical drugs, tumor necrosis factor inhibitors, juvenile idiopathic arthritis, therapy withdrawal, long-term remission, clinically inactive disease

In children and adolescents with temporomandibular disorder assembled with juvenile idiopathic arthritis - no association were found between pain and TMJ deformities using CBCT

BackgroundChildren and adolescents with juvenile idiopathic arthritis (JIA) may suffer from temporomandibular disorder (TMD). Due to this, imaging diagnosis is crucial in JIA with non-symptomatic TM joint (TMJ) involvement. The aim of the study was to examine the association between clinical TMD signs/symptoms and cone-beam computed tomography (CBCT) findings of TMJ structural deformities in children and adolescents with JIA.MethodsThis cross-sectional study is part of a longitudinal prospective multi-centre study performed from 2015–2020, including 228 children and adolescents aged 4–16 years diagnosed with JIA, according to the International League of Associations for Rheumatology (ILAR). For this sub-study, we included the Bergen cohort of 72 patients (32 female, median age 13.1 years, median duration of JIA 4.5 years). Clinical TMD signs/symptoms were registered as pain on palpation, pain on jaw movement, and combined pain of those two. The severity of TMJ deformity was classified as sound (no deformity), mild, or moderate/severe according to the radiographic findings of CBCT.ResultsOf 72 patients, 21 (29.2%) had pain on palpation at and around the lateral pole, while 41 (56.9%) had TMJ pain upon jaw movement and 26 (36.1%) had pain from both. Of 141 TMJs, 18.4% had mild and 14.2% had moderate/severe structural deformities visible on CBCT. CBCT findings were not significantly associated with either the pain on palpation or the pain on jaw movement. A significant difference was found between structural deformities in CBCT and the combined pain outcome (pain at both palpation and movement) for both TMJs for the persistent oligoarticular subtype (p = 0.031).ConclusionsThere was no association between painful TMD and CBCT imaging features of the TMJ in patients with JIA, but the oligoarticular subtype of JIA, there was a significant difference associated with TMJ pain and structural CBCT deformities.

The main factors, associated with incomplete vaccination againts measels, parotitis, rubella, and diphtheria in 170 juvenile idiopathic arthritis patients: the results of prospective pilot study

Background. Patients with juvenile idiopathic arthritis (JIA) may have incomplete vaccination againts different vaccines leads to lower protective levels of anti-vaccine antibodies.The aim of the study – to evaluate the rate and the main factors of incomplete vaccination against measels, parotitis, rubella (MMR), and diphtheria in JIA patients.Methods. In the present study were included data 170 JIA (55 boys and 115 girls) aged from 2 to 17 years, who received scheduled vaccination before the age of 2 years and before JIA onset against measles, parotitis, diphtheria and rubella. Incomplete vaccination means the reduced number of vaccine to age. In all patients the IgG anti-vaccine antibodies levels were detected with ELISA. Data presented with odds ratio ()OR) with 95 confidence interval (CI).Results. Incomplete vaccination against MMR was in 50 (32.5%) of children less than 6 years. Incomplete vaccination against diphtheria was in 6/16 (37.5%) of children less than 6 year, in 53/110 (48.2%) of children aged 6–14 years and in 26/44 (59.1%) of the JIA patients more than 14 years. The main predictors in logistic regression for incomplete vaccination for MMR were: onset age <4 years (OR=12.2 [95% CI: 5.0–28.9]; p=0.0000001), JIA duration >3.1 years (OR=4.4 [95% CI: 2.0–9.9]; p=0.0002), methotrexate duration >3 years (OR=5.7 [95% CI 2.7–12.0]; p=0.0000012); biologic treatment (OR=2.5 [95% CI: 1.3–4.9]; p=0.008) and treatment >1 biologic (OR=3.3 [95% CI: 1.1–10.4]; p=0.002); for diphtheria were: JIA duration >3.1 years (OR=3.4 [95% CI: 1.8–6.5]; p=0.0002), methotrexate duration >2.8 years (OR=4.1 [95% CI: 2.1–8.1]; p=0.00004), biologic treatment (OR=2.4 [95% CI: 1.3–4.4]; p=0.006). In the multiple regression only JIA onset age (p=0.00001) and duration of methotrexate (p=0.003) were predictors of incomplete vaccination against MMR. Methotrexate duration (p=0.005) and biologics treatment (p=0.05) were predictors of incomplete vaccination against diphtheria.Conclusion. The main predictor of incomplete vaccination was younger onset age of JIA. Children received more intensive immunosupression usually have scheduled vaccination rarely which leads to increased number of patients without protective antibody levels. These facts indicate the attitude of physicians parents to vaccination in immunocompromised children. Further investigations required for assessment of safety of vaccinations in children with rheumatic diseases may be a factor for changing this prejudice.

AB0746 THE ASSOCIATION BETWEEN PRESARCOPENIA AND BONE MINERAL DENSITY IN ADULT PATIENTS WITH JUVENILE IDIOPATHIC ARTHRITIS

Background:The importance of presarcopenia (low lean mass) in clinical practice is accompanied by a high risk of adverse effects such as early disability, reduced quality of life, and increased mortality.Objectives:The aim of the study was to assess the link between bone mineral density (BMD) and the state of the muscular system in adult patients with juvenile idiopathic arthritis (JIA).Methods:The study was performed in Oleksandrivska Clinical Hospital of Kyiv, Ukraine, where adult patients were transferred from pediatric rheumatologists. Inclusion criteria: patients aged 18-44 years at the time of signing the informed consent; diagnosis of JIA in childhood, verified according to ILAR criteria, duration of JIA >3 years. According to the European Working Group on Sarcopenia in the Elderly (EWGSOP) 2019, patients with a decrease in muscle mass alone were diagnosed with presarcopenia. The BMD and muscle tissue were determined in standard localizations using dual X-ray absorptiometry (DXA).Results:The study included 26 adult patients with JIA, including 10 male patients and 16 female patients. The mean age at the time of examination was 22.3 ± 8.15 years; the mean age at the onset of the disease was 9.04 ± 4.9 years. According to the ILAR classification, patients had the following variants of JIA: 3 patients with RF-negative polyarticular variant, 8 patients with persistent oligoarthritis, 4 patients with extended oligoarthritis, 6 patients with RF-positive polyarthritis variant, and 5 patients with systemic JIA. According to the EWGSOP, 2019 reduced muscle mass was calculated by skeletal muscle index (SMI); the cut-off points were considered by SMI <7 kg/m2 for male, <6 kg/m2 for female. Patients were divided into two groups depending on the presence or absence of presarcopenia. The first group (1-st group) included 16 patients with reduced muscle mass (SMI – 5,22± 0,72 kg/m2), and the second group (2-nd group) included 10 patients without reduced muscle mass (SMI – 8,05± 0,94 kg/m2). It was found that the height and weight of patients in the group of presarcopenia was lower than in the group without a low lean mass (height 1,6±0,07 m vs 1,7±0,09 m, t=-2,53; p=0,01; weight 55,06±8,3 kg, 70,0±10,8 kg, t=-3,9; p=0,0007, respectively). The age of patients (25,3±10,1 and 21,3±5,9 years for 1-st and 2-nd groups respectively) and the duration of the disease (17,1±9,5 and 10,3±6,1 for 1-st and 2-nd groups respectively) did not differ statistically between the groups. The age of the onset of JIA in both groups also did not differ (7,8±4,5 and 11,5±4,1 for the 1-st and 2-nd group respectively). The following data were obtained by DXA. The patients of 1-st group had statistically reduced BMD in the region of femoral neck - 0,927±0,15 g/cm2 vs 1,179±0,13 g/cm2, t=-3,18; p=0,006; total hip - 0,977±0,16 g/cm2 vs 1,184±0,05 g/cm2, t=-3,05, p=0,0080; total body - 1,080±0,1 g/cm2 vs 1,193±0,15 g/cm2, t=-2,19; p=0,03; and ultra-distal radius - 0,286±0,06 g/cm2 vs 0,482±0,11 g/cm2, t=-3,60; p=0,007. The BMD in the region of lumbar spine did not differ in two groups - 1,152±0,16 g/cm2 vs 1,137±0,17 g/cm2, t=0,21; p=0,8. In the group of presarcopenia there was a visible decrease in the level of the metabolite of vitamin 25(OH)D3, but not statistically significant: 15,5±7,3 nmol/l vs 19,7±8,6 nmol/l, t =1,0; p=0,3. The study has strengths such as first described presarcopenia in young adults with JIA and potential limitations such as mono-center study and a small number of patients.Conclusion:The BMD in the region of total hip, femoral neck, ultra-distal radius, and total body in patients with decreased muscle mass was significantly lower than in patients without low lean mass.

Renal Lesions of Juvenile Idiopathic Arthritis in Children: A Literature Review

The literature review presents current data on the frequency, mechanisms of development, clinical manifestations, diagnosis and treatment of renal AA-amyloidosis and describes different forms of glomerulonephritis (GN) in children with juvenile idiopathic arthritis (JIA). The frequency of AA renal amyloidosis in JIA in children ranges from 0.8% to 2%, in adults with JIA duration of 28.3 years - 8.9%. In recent years, against the background of immunobiological therapy, the incidence of AA-amyloidosis of the kidneys in adults has decreased to 2%. AA-amyloidosis of the kidneys most often develops in children with the systemic form, in adults - with systemic and polyarticular forms of JIA. The first symptom of AA-amyloidosis of the kidneys is isolated proteinuria, which transforms into nephrotic syndrome. The peculiarity of the nephrotic syndrome is the absence of hypercholesterolemia in most cases, combined in some patients with arterial hypertension, hematuria, and impaired renal function. The available literature presents clinical cases of renal GN in children with JIA, viz: ANCA-associated GN, mesangioproliferative GN, including IgA- and IgM-nephropathy, membranous nephropathy, focal-segmental glomerulosclerosis, minimal change disease, extracapillary GN. Most publications are devoted to ANCA-associated HN, which developed in patients with a torpid course and a high degree of activity of polyarticular and systemic forms of JIA. The peculiarity of ANCA-associated HN was the presence of hypercreatininemia and, in almost half of cases, the development of terminal renal failure, despite the ongoing immunosuppressive therapy. The main method confirming the diagnosis of AA-amyloidosis and renal HN is the intravital renal morphological study. The use of immunobiological drugs in renal AA-amyloidosis and HN in children with JIA has therapeutic efficacy.

Alterations of Extracellular Matrix Components in the Course of Juvenile Idiopathic Arthritis.

Juvenile idiopathic arthritis (JIA) is the most common group of chronic connective tissue diseases in children that is accompanied by joint structure and function disorders. Inflammation underlying the pathogenic changes in JIA, caused by hypersecretion of proinflammatory cytokines, leads to the destruction of articular cartilage. The degradation which progresses with the duration of JIA is not compensated by the extent of repair processes. These disorders are attributed in particular to changes in homeostasis of extracellular matrix (ECM) components, including proteoglycans, that forms articular cartilage. Changes in metabolism of matrix components, associated with the disturbance of their degradation and biosynthesis processes, are the basis of the progressive wear of joint structures observed in the course of JIA. Clinical evaluation and radiographic imaging are current methods to identify the destruction. The aim of this paper is to review enzymatic and non-enzymatic factors involved in catabolism of matrix components and molecules stimulating their biosynthesis. Therefore, we discuss the changes in these factors in body fluids of children with JIA and their potential diagnostic use in the assessment of disease activity. Understanding the changes in ECM components in the course of the child-hood arthritis may provide the introduction of both new diagnostic tools and new therapeutic strategies in children with JIA.

Pain sensitivity in young adults with juvenile idiopathic arthritis: a quantitative sensory testing study

BackgroundTo study for the first-time, pain perception, pain sensitivity, and self-reported pain in young adults with long disease duration of juvenile idiopathic arthritis (JIA) compared with controls.MethodsChildren from Central Norway diagnosed with JIA between 1997 and 2004 were included consecutively in a population-based prospective study. Children with onset 1997–2000 were part of the Nordic JIA cohort. Controls were age- and sex-matched. In 2015–2017, study visits with investigator-blinded quantitative sensory testing (QST) comprising cold and warm detection thresholds (CDT/WDT), cold and heat pain thresholds (CPT/HPT), pressure pain threshold (PPT), and a suprathreshold heat pain test were performed. We constructed separate multilevel models for each variable of detection and pain thresholds with interaction between groups and site adjusted for the effect of age and sex.ResultsAmong 96 young adults with JIA, 71% were female, median age was 22.7 years, disease duration was 16.1 years, and 47% had oligoarticular disease. Among 109 controls, 71% were female, and median age was 23.5 years. Participants with JIA had lower pressure pain thresholds (PPTs) (95% CI) compared to controls, upper limb 888 (846,930) versus 1029 (999,1059) kPa and lower limb 702 (670,734) versus 760 (726,794) kPa. Participants with inactive disease had the lowest PPTs and cold pain thresholds (CPTs), compared to those in remission off medication and those with active disease. Minor differences were found regarding CDT/WDT and CPT/HPT in JIA compared to controls. The median (IQR) temperature needed to evoke pain = 6 on a 0–10 numeric rating scale (NRS) in the suprathreshold heat pain tests were lower in JIA than in controls (46 °C (45–47 °C) versus 47 °C (46–48 °C)). We found no associations between self-reported pain and pain thresholds.ConclusionsOur results indicate for the first time that young adults with long disease duration of JIA may have altered pain perception and sensitivity compared to controls. A clinical implication may be the importance of early treatment to quickly achieve pain-free remission and avoid long-term pain sensitization.

Prevalence of and factors associated to chronic kidney disease and hypertension in a cohort of children with juvenile idiopathic arthritis.

We evaluated chronic kidney disease (CKD) (proteinuria or estimated glomerular filtration rate < 60 mL/min/1.73 m2) or hypertension prevalence in 110 children with juvenile idiopathic arthritis (JIA). CKD and hypertension were clustered under the umbrella term of "renal injury". Median age at the last visit was 14 years. Nine out of 110 (8.1%) patients showed renal injury (8 hypertension, 1 proteinuria). Patients with renal injury presented higher age at last visit, longer duration of active JIA, shorter intervals free from JIA relapses, longer duration of non-steroidal anti-inflammatory drugs (NSAIDs) treatment but with similar cumulative NSAIDs dose and higher rate of methotrexate (MTX) prescription, longer time of MTX administration, and higher cumulative MTX dose compared to patients without renal injury. At the last visit, patients with and without renal injury presented similar prevalence of active disease. The cumulative proportion of patients free from renal injury at 240 months since JIA onset was 40.72% for all population; while the cumulative proportion was 23.7% for patients undergoing NSAIDs+MTX treatment and 100% for those undergoing NSAIDs (p = 0.039) treatment.Conclusion:About 8% of the children with JIA develop hypertension or CKD. The main risk factor was longer exposure to both NSAIDs and MTX due to a more severe form of the disease. What is Known •Anecdotal reports showed that rarely juvenile idiopathic arthritis (JIA) could present renal involvement due to prolonged and uncontrolled inflammation (renal amyloidosis) or to long exposure to anti-rheumatic drugs. •No cohort studies investigated renal health in children with JIA. What is new •About 8% of the children with JIA developed hypertension or chronic kidney disease. •The main risk factor was long exposure to non-steroidal anti-inflammatory drugs and methotrexate for patients suffering from a more severe form of the disease. •In JIA patients, periodic evaluation of renal function, blood pressure and proteinuria should be warranted.

The effects on Oral Related Quality of Life induced by periodontitis in patients with juvenile idiopathic arthritis

The objective of study was to evaluate the impact of periodontitis on the health-related quality of life (HRQoL) in patients affected by juvenile idiopathic arthritis (JIA). Sixty consecutive patients with JIA with or without periodontitis and 33 healthy control subjects were enrolled in the study. The demographic data, disease activity and clinical characteristics were obtained from all patients. HRQoL and disability was assessed by two questionnaires, the Italian version of the Childhood Health Assessment Questionnaire (C-HAQ) and the Child Perception Questionnaire (CPQ11-14). Possible determining factors of periodontitis comprised demographic and disease characteristics and HRQOL scores that were assessed by uni- and multivariable logistic regression analysis. Compared to patients without periodontitis, JIA patients with periodontitis presented higher disability and lower HRQOL scores. The multivariable logistic regression analysis highlighted that female subjects (OR 1.4) or a JIA duration over 4.1 years (OR 2.6), higher C-HAQ and CPQ11-14 scores (OR 2.8 – 2.9) were the greatest determining factors for periodontitis. JIA patients with periodontitis presented lower HRQoL compared to JIA patients without periodontitis. Periodontitis was strongly associated with JIA duration and activity and negatively influenced the HRQoL of JIA patients.

Preservation of Postvaccinal Immunity to Measles, Rubella, Parotitis, Hepatitis B and Diphtheria in Patients With Juvenile Idiopathic Arthritis Who Undergone Planned Immunization Under the Age of Two: Preliminary Results of Cross-Sectional Study

Background. Patients with juvenile idiopathic arthritis (JIA) can have low levels of antibodies to vaccine antigens due to immunologic features of the main disease, disruptions in vaccination schedule and immunosuppressive drugs administration Objective. The aim of the study was to examine the status of postvaccinal immunity and determine the factors associated with preservation of protective level of antibodies in patients with JIA. Methods. This cross-sectional study included patients with JIA at the age from 2 to 17 years old vaccinated under the age of two (before JIA) against measles, rubella, parotitis, hepatitis B and diphtheria. Levels of IgG to vaccine antigens were measured by enzyme immunoassay. The minimum protective level of anti-measles IgG was esteemed as 0.18 IU/ml, antibodies to rubella — 10 IU/ml, for parotitis — COI > 1.0, for hepatitis B — 10 mIU/ml, antibodies to diphtheria — 0.09 IU/ml. Results. The study included 90 patients with JIA (71% of girls) at the age (median) 11.3 (7.5; 14.9) years. The age of JIA manifestation was 6.0 (4.0; 8.0) years, disease duration — 4.0 (2.0; 7.3) years. Glucocorticosteroids administration in anamnesis or at study entry was recorded in 24/88 (27%) patients, methotrexate — 81/88 (92%), genetically engineered biologic drugs — 54/89 (61%). Protective level of antibodies to measles virus was revealed in 45 (50%) children with JIA, to rubella virus — in 88 (98%), to parotitis — in 68 (76%), to hepatitis B — in 49 (54%), to diphtherial anatoxin — in 45 (50%). The decrease of postvaccinal immunity level was associated with JIA duration and glucocorticosteroids administration (against diphtheria) duration, as well as drop-out immunization (against measles). Conclusion. Major part of children with JIA have no protection against measles, parotitis, hepatitis B or diphtheria. High risk of progression of such vaccine-preventable diseases in these children demands development of individual programs of immunization.

Visual Function And Quality Of Life In A Cohort Of Swedish Children With Juvenile Idiopathic Arthritis.

PurposeTo evaluate quality of life (QoL) in children with juvenile idiopathic arthritis (JIA).MethodsForty children with a mean age of 7.9 years were included. The children underwent an ophthalmological examination and completed questionnaires on physical function (CHAQ) and vision-related (VR) QoL (EYE-Q).ResultsNo differences regarding visual acuity (VA), refraction, intraocular pressure or physical or VRQoL were found between those with JIA without (n=33) and those with JIA-associated uveitis (n=7). When comparing physical function measured by CHAQ disability index and JIA subtype, a difference was found; children with polyarthritis scored the worst (p=0.0098). Children with subnormal VA scored worse on EYE-Q compared with those with normal VA (p=0.013). We found correlations between duration of JIA and CHAQ disability index (r=−0.42, p=0.0007) and CHAQ well-being (r=−0.34, p=0.022).ConclusionThis study indicates the importance of measuring not only physical function but also VRQoL in children with JIA and JIA-associated uveitis.

The impact of temporomandibular joint arthritis on functional disability and global health in patients with juvenile idiopathic arthritis.

The objective of the study was to evaluate the impact of temporomandibular joint (TMJ) arthritis on the functional disability and quality of life in patients affected by juvenile idiopathic arthritis (JIA). Sixty-two consecutive patients with JIA with or without TMJ arthritis and 35 healthy control subjects were enrolled in the study. The demographic data, disease activity and clinical characteristics were obtained from all patients. The functional disability was assessed using the Italian version of the Childhood Health Assessment Questionnaire (C-HAQ). The oral health-related quality of life (OHRQoL) was assessed using the Child Perception Questionnaire (CPQ11-14). Possible determining factors of TMJ arthritis comprised demographic, disease characteristics and scores derived from questionnaires that were assessed by a uni and multivariable logistic regression analysis. Compared with patients without TMJs arthritis, JIA patients with TMJ arthritis presented higher functional disability. The multivariable logistic regression analysis performed showed that female subjects (OR = 1.5, P = 0.041), with a JIA duration over 3.9 years (OR = 2.7, P = 0.033) and presenting higher C-HAQ and CPQ11-14 scores (OR = 2.7, P = 0.012 and OR = 2.9, P = 0.015, respectively) were the greatest determining factors for TMJ arthritis. JIA patients with TMJ arthritis presented higher functional disability and lower OHRQoL scores compared with JIA patients without TMJ arthritis. TMJ arthritis was strongly associated with JIA duration and activity, especially in female patients.