Course Of Juvenile Idiopathic Arthritis 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.

Роль вітаміну D при ювенільному ідіопатичному артриті

Considering the role of vitamin D in mineral metabolism and its extracellular effects, including immunomodulation with a tendency to suppress the immune response, there is significant interest in determining its role in developing autoimmune diseases, including juvenile idiopathic arthritis (JIA). Purpose - to determine the role of vitamin D in the development and course of JIA based on a systematic analysis of literature sources over the last 7 years. A search was conducted on PubMed for articles on the role of vitamin D in the development and course of JIA, using combinations of the following terms: “vitamin D” and “juvenile idiopathic arthritis”. The review included scientific publications with available full texts published from January 2017 to August 2023. The analysis results showed significant variations in the level of 25(OH)D among patients with JIA, and the vitamin D status in the majority of JIA patients was not optimal. However, the percentage of patients with suboptimal levels and vitamin D deficiency, according to the majority of studies, was not more significant than in the general population. Nevertheless, a correlation was found between low 25(OH)D concentration and high activity of JIA. Additional vitamin D supplementation did not impact the reduction of JIA activity or the improvement of indicators of bone mineral density. However, some publications emphasize the positive effect of sun exposure in reducing the risk of JIA. Further research is needed to clarify the necessity of additional vitamin D supplementation involving a larger number of patients, standardization, selection of optimal doses, and treatment duration. No conflict of interests was declared by the authors.

The dual role of body mass index on Juvenile Idiopathic Arthritis course: a pediatric experience.

Despite the well-known role of obesity as risk factor for Juvenile Idiopathic Arthritis (JIA) severity, emerging but limited evidence suggested a similar role for underweight. We investigated the role of body mass index (BMI) across its full spectrum in a cohort of children with JIA.We retrospectively studied 113 children with JIA classified according to the International League of Association for Rheumatology (ILAR) criteria attending our Rheumatology Clinic. The patients underwent a comprehensive evaluation including both clinical and biochemical assessments. According to BMI Z-score, the cohort was divided into five groups as underweight, normal weight, overweight (OW), obesity (OB), and severe OB. Disease activity was calculated by Juvenile Arthritis Disease Activity Score 10 (JADAS-10) joint reduced count and relapses were defined according to Wallace criteria.The mean age of the cohort was 7.43 ± 4.03years. The prevalence of underweight, normal weight, OW, OB, and severe OB was 7.2%, 54.1%, 10.8%, 17.1%, and 10.8%, respectively. Significant higher ferritin levels and erythrocyte sedimentation rate values were found in patients with severe OB and underweight compared to subjects belonging to normal weight, OW, and OB groups. A greater JADAS-10 score was observed in underweight patients and in those with severe OB than other groups. The relapse rate was higher in patients with severe OB and underweight compared to other groups. Conclusions: Both underweight and OB might negatively affect JIA course. Weight control is fundamental in children with JIA to avoid a more unfavourable course of the disease. What is Known: • Obesity represents a well-known risk factor for JIA severity. • The role of underweight in children with JIA is still poorly explored. What is New: • As observed in children with obesity, underweight young patients with JIA seem to experience a more severe JIA course. • Healthy lifestyle promotion in children with JIA is a crucial step in the management of the disease.

Ultrasound and MRI of the foot in children and adolescents newly diagnosed with juvenile idiopathic arthritis.

To evaluate the spectrum of inflammatory features in foot joints which may be detected on routinely performed ultrasound (US) and magnetic resonance imaging (MRI) in children newly diagnosed with juvenile idiopathic arthritis (JIA). Two groups of children hospitalized in a reference center for rheumatology, newly diagnosed with JIA and suspected of foot involvement in the course of JIA were included in this retrospective study. In the first group of 47 patients aged 1-18 years, the imaging was restricted to US. The second group of 22 patients aged 5-18 years underwent only non-contrast MRI of the foot. The most frequent pathologies seen on US included effusion and synovial thickening in the first metatarsophalangeal joint (MTP1), followed by the tibiotalar joint. Synovial hyperemia on color Doppler US images was present most frequently in the Chopart and midtarsal joints (64%; 7/11 cases), followed by the tibiotalar joint (45%; 5/11), and MTP2-5 joint synovitis (40%; 4/10). Grade 3 hyperemia was present only in four cases; grades 1 and 2 were detected in the majority of cases. On MRI, bone marrow edema was the most frequent pathology, found mostly in the calcaneus (45%; 10/22 cases), while alterations of the forefoot were rare. No cases of bursitis, enthesitis, cysts, erosions or ankylosis were diagnosed in either of the analyzed groups. Routine US of the foot is recommended for early detection of its involvement in JIA in daily clinical practice. Although MRI can identify features of various JIA stages, it is particularly useful for the detection of bone marrow alterations.

ВЫЯВЛЕНИЕ НАРУШЕНИЙ ПСИХИЧЕСКОГО ЗДОРОВЬЯ ПРИ ЮВЕНИЛЬНОМ ИДИОПАТИЧЕСКОМ АРТРИТЕ С ХРОНИЧЕСКИМ БОЛЕВЫМ СИНДРОМОМ

Mental health disorders in pediatric rheumatologists’ practice are often unrecognized and insufficiently taken into account by pediatric rheumatologists when managing patients suffering from juvenile idiopathic arthritis (JIA). The chronic pain syndrome, which complicates the course of JIA, largely has a psychosomatic basis and is associated both with the severity of mental disorders in the patients themselves and with the characteristics of parent-child relationships. The purpose of the research was to study the severity of manifestations of mental disorders, emotional regulation and parent-child relationships in pediatric patients with JIA with chronic pain syndrome in comparison with patients with acne. Materials and methods used: a single-center simultaneous study of adolescents aged 11 to 17 y/o was conducted in Oct.-Dec. 2022. Using a visual analogue scale, the severity of pain was assessed separately by the participants in the study and their parents; patients assessed their general condition, whilst the physician determined the overall assessment of the current activity of the disease. All of the participants had completed the Difficulties in Emotion Regulation Scale (DERS), Parental bonding instrument (PBI) and Strengths and Difficulties Questionnaire (SDQ) questionnaires. Results: the main group consisted of 30 suffering from JIA with chronic pain syndrome. The comparison group consisted of 40 with acne. In patients with JIA, the values in the scales “Behavioral problems” (p=0.001), “Hyperactivity” (p=0.001), “Problems with peers” (p=0.001), “Emotional detachment” (assessment of mothers and fathers, p=0.001) and “Hyper care” (assessment of mothers and fathers, p=0.001) were statistically significantly lower, whilst higher in the values for “Prosocial behavior” (p=0.026), “Awareness of own emotions” (p=0.001), “Emotional warmth” (assessment of mothers and fathers, p=0.001) and “Encouraging independence” (assessment of mothers and fathers, p=0.001). Conclusion: JIA patients with chronic pain syndrome demonstrated more favorable mental health outcomes compared to patients with acne, which is traditionally considered as a factor in the mental adjustment disorder of adolescents that negatively affects the emotional state, self-esteem and the quality of life.

Presence of uveitis as indicator of juvenile idiopathic arthritis severity: results of a retrospective cohort study

BACKGROUND: Juvenile idiopathic arthritis is the most common rheumatic disease in children. A frequent extra-articular manifestation of juvenile idiopathic arthritis is uveitis, which is a serious clinical diagnostic problem in routine pediatric practice. Among the known risk factors for uveitis are the early age of the juvenile idiopathic arthritis onset, oligoarticular subtype, seropositivity by antinuclear factor.
 AIM: to evaluate the influence of presence of uveitis on the course of juvenile idiopathic arthritis.
 MATERIALS AND METHODS: A single-center retrospective study included 520 patients with uveitis. The analysis was carried out among patients who developed (n = 116) and did not develop (n = 404) uveitis. The minimum follow-up period was 2 years, for patients who did not develop uveitis.
 RESULTS: Uveitis was diagnosed in 116 (22.3%) children with juvenile idiopathic arthritis. Most often, uveitis occurred in patients with oligoarthritis and psoriatic arthritis. When comparing the features of the articular status of patients with juvenile idiopathic arthritis who developed and did not develop uveitis, a lower frequency of involvement of the cervical spine, temporomandibular, shoulder, elbow, wrist, proximal and distal interphalangeal joints, hip, talus-heel joint, as well as a smaller number of active joints in children with uveitis was found. Patients with uveitis received methotrexate therapy more often, cumulative doses of corticosteroids were lower, the frequency of prescribing genetically engineered biological drugs was approximately the same in both groups. Remission of arthritis was achieved more often, but the proportion of children who developed an exacerbation was higher. When calculating the risk factors of uveitis by binary logistic regression, it was found that the main predictors of uveitis were oligoarthritis, the number of active joints 8, seropositivity by antinuclear factor and recurrent course of arthritis. The difference in the frequency of achieving remission may be due to more aggressive systemic therapy in the presence of uveitis.
 CONCLUSIONS: Children with uveitis have a more severe course of juvenile idiopathic arthritis and may require more aggressive immuno-suppressive therapy. Further studies are required to determine the prognostic role of uveitis in the course and outcomes of juvenile idiopathic arthritis.

Systemic juvenile idiopathic arthritis in the pediatric practice of Donetsk region

Juvenile idiopathic arthritis with systemic onset is a special, rare and the most severe variant of juvenile idiopathic arthritis. The article analyzes the clinical features of the onset and course of juvenile idiopathic arthritis with systemic onset in children living in the ecologically disadvantaged Donetsk region and the efficacy of therapy. Clinical cases are described. According to its clinical manifestations, the systemic variant of juvenile idiopathic arthritis is characterized by the severity of the general inflammatory response, a bright clinical picture, severe damage to internal organs, the development of polyserositis, can lead to the development of life-threatening conditions, such as macrophage activation syndrome, and also leads to the formation of deforming arthritis with early disability of the sick child. The relevance of studying the problem of juvenile idiopathic arthritis with a systemic onset is related to the late diagnosis of the disease, because at the onset of the disease there may be no joint syndrome, and therefore it is impossible to use the criteria of the International League of Rheumatology Associations to verify the diagnosis, which leads to diagnostic errors. Nonsteroidal anti-inflammatory drugs, glucocorticosteroids, and immunosuppressants are used for treatment. The prescription of genetic engineering biological therapy, the choice of the drug, is carried out according to the recommendations of the American College of Rheumatology, depending on the preference for systemic or joint manifestations of the disease. But the question of the optimal approach to regimens of dose reduction, duration of biological therapy, and rules for its withdrawal remains open. Until now, the optimal approach to the treatment of juvenile idiopathic arthritis with a systemic onset is unknown. To date, the issue of treatment in patients with pharmacoresistant variants and persistent course of the disease has not been solved. Therefore, further in-depth study of this problem, optimization of the diagnostic algorithm and an individual approach to therapy are needed.

Impaired cardiorespiratory and neuromuscular fitness in children and adolescents with juvenile idiopathic arthritis: a cross-sectional case–control study in the era of biologic drug therapies

BackgroundIn recent years, biologic drug therapies have altered the course of juvenile idiopathic arthritis (JIA) possibly also improving the patients’ physical fitness. However, studies measuring both cardiorespiratory and muscular fitness in children with JIA are sparse and have failed to show consistent results.Our aim was to assess both cardiorespiratory and neuromuscular fitness and contributing factors in children and adolescents with JIA in the era of biologic drug therapies.MethodsThis cross-sectional study consisted of 73 JIA patients (25 boys, 48 girls) aged 6.8- 17.5 years and 73 healthy age- and sex-matched controls, investigated in 2017–2019. Cardiorespiratory fitness was assessed by maximal ergospirometry and neuromuscular fitness by speed, agility, balance, and muscle strength tests.ResultsMeans (± SD) of maximal workload (Wmax/kg) and peak oxygen uptake (VO2peak/kg,) were lower in JIA patients than in controls (Wmax/kg: 2.80 ± 0.54 vs. 3.14 ± 0.50 Watts, p < 0.01; VO2peak/kg: 38.7 ± 7.53 vs. 45.8 ± 6.59 ml/min/kg, p < 0.01). Shuttle-run, sit-up and standing long jump test results were lower in JIA patients than in controls (p < 0.01). Mean (± SD) daily activity was lower (89.0 ± 44.7 vs. 112.7 ± 62.1 min/day, p < 0.05), and sedentary time was higher (427 ± 213 vs. 343 ± 211 min/day, p < 0.05) in JIA patients compared to controls. Physical activity and cardiorespiratory or neuromuscular fitness were not associated with disease activity.ConclusionsJIA patients were physically less active and had lower cardiorespiratory and neuromuscular fitness than their same aged controls with no JIA. Therefore, JIA patients should be encouraged to engage in physical activities as a part of their multidisciplinary treatment protocols to prevent adverse health risks of low physical activity and fitness.

Revising diagnosis of juvenile idiopathic arthritis in adults: a single-center retrospective study

The study aimed to assess how many adult patients with juvenile idiopathic arthritis (JIA) treated with biologics fulfill classification criteria for adult rheumatic diseases and to evaluate the course of JIA in adulthood. 138 patients with JIA over 18 years old treated with biologics were included in a cross-sectional observative study. Among 138 adult patients with JIA treated with biologics, 81 patients remained with JIA diagnosis. 57 patients were rediagnosed. 31 patients met the criteria for spondyloarthropathy, among them 18 patients for ankylosing spondylitis, 10 patients for psoriatic arthritis, and 3 patients for non-radiographic axial spondyloarthritis. Rheumatoid arthritis was diagnosed in 24 patients and adults’ Still disease in 2 patients. 84 patients of all adults with JIA received one biologic agent, 40 received two biologic agents, and 14 received three or more biologic therapies. 10 patients received biologic agents out of recommendations for JIA. Of the adult JIA patients treated with biologics, 41% met the classification criteria for adult inflammatory diseases. Spondyloarthropathy and rheumatoid arthritis were most commonly diagnosed. Nearly 40% of adult JIA patients required at least one modification of biological treatment. Therefore, it is worth considering a revision of JIA to adult-onset inflammatory disease entities, as it broadens the spectrum of disease-modifying drugs.

Емоційна складова якості життя пацієнтів з ювенільним ідіопатичним артритом

For children with juvenile idiopathic arthritis (JIA), the quality of life (QoL) emotional component is influenced by numerous factors: the arthritis subtype, disease duration, and activity, patient’s treatment, patient’s physical condition, and pain level, also his age, and sex. However, it’s important to determine the emotional component in the structure of QoL in children with different JIA subtypes (polyarthritis, oligoarthritis, and uveitis-associated arthritis) and features of psychological adaptation in modern conditions. Purpose - to determine both the emotional component of QoL in patients with JIA and their emotional condition considering the disease subtype, its duration, and the therapy complex. Materials and methods. The study was carried out at the SI «Institute for Children and Adolescents Health Care of the NAMS of Ukraine», Kharkiv, from November 2020 to November 2021. The assessment was provided by JADAS27, functional state by CHAQ, QoL according to PedsQLTM 4.0 Generic Core Scales, and emotional state according to the Montgomery-Asberg scale (MADRS) for depression assessment and clinical indicators. Statistical processing of the material was carried out using parametric and non-parametric methods, the critical level of significance for statistical testing hypotheses comparing groups was set at 0.05. Results. The 118 patients with JIA were examined, of them 47 patients with polyarticular, 43 patients with oligoarticular, and 28 patients with JIA-u subtypes. The study involved 77 girls and 41 boys aged 2 to 18 years (133.3±4.6 months). The majority (112 patients) received methotrexate therapy, 30 of them - methotrexate in combination with immunobiological therapy, 6 - sulfasalazine. The overall QoL in the group of children with JIA was at the level of 70.9±1.4 points for the last month and 72.6±1.4 points for the last week without significant difference, and the emotional component in the group as a whole was significantly higher for the last month - 73.1±1.6 points, while during the hospital stay it decreased to 66.3±1.7 points (p≤0.05). According to the results of the assessment of emotional state by the MADRS questionnaire, children aged 8 years and older did not have a depressive episode - 6.02±0.72 points. No significant differences were observed for HRQoL and emotional component in groups with different variants of arthritis and depending on age. However, certain results with a decrease in QoL and emotional state were observed in children with polyarthritis and uveitis-associated variant of JIA. The duration of the disease and treatment affected the QoL and emotional state, especially in the first year (QoL = 62.5±3.8 points for the last month). Correlations between MADRS and emotional state according to PedsQL were indirect and strong both for the last week and for the last month (r=-0.821; r=-0.784; p≤0.05). MADRS and total PedsQL scores also had indirect, medium strength correlations for the study periods (r=-0.558; r=-0.528; p≤0.05). Conclusions. At the beginning of the disease children with JIA have the reduction of QoL indicators with the emotional component. Such results depend on the course of JIA, which predicts the formation of emotional depressive disorders in some of them. The first year of the disease is the most vulnerable for children with polyarthritis, and for children with JIA-u increased disease duration enhances symptoms of emotional disturbances. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

The Role of Interleukin-17 in Juvenile Idiopathic Arthritis: From Pathogenesis to Treatment.

Background and Objectives: Interleukin-17 (IL-17) is a cytokine family consisting of six members and five specific receptors. IL-17A was the first member to be identified in 1993. Since then, several studies have elucidated that IL-17 has predominantly pro-inflammatory activity and that its production is involved in both the defense against pathogens and the genesis of autoimmune processes. Materials and Methods: In this review, we provide an overview of the role of interleukin-17 in the pathogenesis of juvenile idiopathic arthritis (JIA) and its relationship with IL-23, the so-called IL-23-IL-17 axis, by reporting updated findings from the scientific literature. Results: Strong evidence supports the role of interleukin-17A in the pathogenesis of JIA after the deregulated production of this interleukin by both T helper 17 (Th17) cells and cells of innate immunity. The blocking of IL-17A was found to improve the course of JIA, leading to the approval of the use of the human anti-IL17A monoclonal antibody secukinumab in the treatment of the JIA subtypes juvenile psoriatic arthritis (JPsA) and enthesitis-related arthritis (ERA). Conclusions: IL-17A plays a central role in the pathogenesis of JIA. Blocking its production with specific biologic drugs enables the effective treatment of this disabling childhood rheumatic disease.

Increased Relapse Rate During COVID-19 Lockdown in an Italian Cohort of Children With Juvenile Idiopathic Arthritis.

ObjectiveChanges of routine disease management associated with COVID‐19 lockdown might have potentially affected the clinical course of juvenile idiopathic arthritis (JIA). The aim of our study was to assess the rate of disease flare before and during COVID‐19 lockdown to investigate its impact on disease course in children with JIA.MethodsA single‐center retrospective study was conducted, including patients presenting with inactive JIA between September 1, 2018 and March 9, 2019 (group A) and between September 1, 2019 and March 9, 2020 (group B). For each patient, demographic and clinical data were collected. The rate of JIA flare from March 10, 2019 to June 30, 2019 for group A and from March 10, 2020 to June 30, 2020 for group B was compared.ResultsGroup A included 126 patients, and group B 124 patients. Statistical analysis did not show significant differences among the 2 cohorts with respect to age, sex, age at JIA onset, JIA subtype, co‐occurrence of uveitis, antinuclear antibody positivity, and past or ongoing medications. The rate of disease flare during lockdown at the time of the first COVID‐19 pandemic wave was significantly higher in comparison to the previous year (16.9% versus 6.3%; P = 0.009).ConclusionOur study showed that COVID‐19 lockdown was associated with a higher rate of joint inflammation in children with JIA. This finding has a considerable clinical implication, as restrictive measures may be necessary in order to contain pandemics. Our data highlight the need for rearrangement in the home and health care management of children with JIA during lockdowns.

GAAGs, COMP, and YKL-40 as Potential Markers of Cartilage Turnover in Blood of Children with Juvenile Idiopathic Arthritis Treated with Etanercept—Relationship with ADAMTS4, ADAMTS5, and PDGF-BB

We quantified galactosaminoglycans (GAAGs), oligomeric cartilage matrix protein (COMP), and human cartilage glycoprotein 39 (YKL-40) in blood obtained from juvenile idiopathic arthritis (JIA) before and during 2-year treatment with etanercept (ETA), as potential biomarkers of cartilage extracellular matrix (ECM) dysfunction and indicators of efficacy of biologic therapy. We also evaluated the relationship of the mentioned markers with the factors that regulate their metabolism, disintegrin and thrombospondin motif metalloproteinases 4 (ADAMTS4), ADAMTS5, and platelet-derived growth factor BB (PDGF-BB). Methods: We studied 38 children diagnosed with JIA and 45 healthy children. We quantified GAAGs by assessing the concentration of unsaturated disaccharide units formed by digestion of isolated glycosaminoglycans with chondroitinase ABC, while COMP, YKL-40, and PDGF-BB were quantified using immunoenzymatic methods. Results: Compared to the control group, GAAGs and COMP levels were significantly lower, while YKL-40 levels were higher in the blood of patients with aggressive JIA, qualified for ETA treatment. ETA therapy leading to clinical improvement simultaneously promoted normalization of COMP and YKL-40 levels, but not GAAGs. After 24 months of taking ETA, glycan levels were still significantly lower, relative to controls. GAAGs, COMP, and YKL-40 levels were significantly influenced by ADAMTS4, ADAMTS5, and PDGF-BB levels both before and during ETA treatment. Conclusions: The dynamics of changes in marker concentrations during treatment seem to indicate that measurement of COMP and YKL-40 levels can be used to assess the chondroprotective biological efficacy of therapy. In contrast, changes in GAAGs concentrations reflect systemic extracellular matrix transformations in the course of JIA.

Plasma Glycosaminoglycans in Children with Juvenile Idiopathic Arthritis Being Treated with Etanercept as Potential Biomarkers of Joint Dysfunction.

We assessed the effect of two-year etanercept (ETA) therapy on the metabolism of the cartilage extracellular matrix (ECM) in patients with juvenile idiopathic arthritis (JIA). Methods: We performed a quantitative evaluation of glycosaminoglycans (GAGs) (performed by the multistage extraction and purification method) in blood obtained from patients before and during 24 months of ETA treatment, as potential biomarker of joint dysfunction and indicators of biological effectiveness of therapy. Since the metabolism of GAGs is related to the activity of proteolytic enzymes and prooxidant–antioxidant factors, we decided to evaluate the relationship between GAGs and the levels of metalloproteinases (MMP), i.e., MMP-1 and MMP-3 (using immunoenzymatic methods), as well as the total antioxidative status (TAS) (using the colorimetric method) in blood of the JIA patients. Results: When compared to the controls, GAGs and TAS concentrations were significantly lower in patients with an aggressive course of JIA qualified for ETA treatment. MMP-1 and MMP-3 levels were significantly higher versus control values. An anti-cytokine therapy leading to clinical improvement does not lead to the normalization of any of the assessed parameters. GAGs concentration is significantly related to MMP-1, MMP-3, TAS, TOS, and CRP levels. Conclusion: The results of the present study indicate the necessity of constant monitoring of the dynamics of destructive processes of articular cartilage in children with JIA. We suggest that GAGs may be a useful biomarker to assess the clinical status of the extracellular matrix of joints.

The Effects of TNF-α Inhibition on the Metabolism of Cartilage: Relationship between KS, HA, HAPLN1 and ADAMTS4, ADAMTS5, TOS and TGF-β1 Plasma Concentrations in Patients with Juvenile Idiopathic Arthritis.

We assessed the effect of 24-month anti-tumor necrosis factor alpha (TNF-α) treatment on the remodeling of the cartilage extracellular matrix (ECM) in patients with juvenile idiopathic arthritis (JIA). Methods: Quantitative evaluation of keratan sulfate (KS), hyaluronic acid (HA), hyaluronan and proteoglycan link protein 1 (HAPLN1), as potential biomarkers of joint dysfunction, and the levels of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) 4 and 5, total oxidative status (TOS) and transforming growth factor (TGF-β1) was performed (using immunoenzymatic methods) in blood obtained from patients before and after 24 months of etanercept (ETA) treatment. Results: When compared to the controls, KS, HA and HAPLN1 levels were significantly higher in patients with an aggressive course of JIA qualified for ETA treatment. An anti-cytokine therapy leading to clinical improvement promotes the normalization only of the HA level. Proteolytic and pro-oxidative factors, present in high concentrations in patients before the treatment, correlated with HAPLN1, but not with KS and HA levels. In these patients, negative correlations were found between the levels of TGF-β1 and KS, HA and HAPLN1. Conclusion: The anti-TNF-α therapy used in patients with JIA has a beneficial effect on ECM cartilage metabolism, but it does not completely regenerate it. The changes in the plasma HA level during the anti-cytokine therapy suggest its potential diagnostic utility in monitoring of disease activity and may be used to assess the efficacy of ETA treatment.

Сироватковий цистатин С як маркер ниркової дисфункції в дітей з ювенільним ідіопатичним артритом

An accurate assessment of the estimated glomerular filtration rate (eGFR) is important for early detection of chronic kidney disease, control of nephrotoxicity, and dose adjustment of drugs. To date, there has been only one cohort retrospective study of the prevalence of chronic kidney disease in children with juvenile idiopathic arthritis (JIA). Purpose - to determine the level of serum cystatin C and, on its basis, the state of eGFR depending on the form of the clinical course, degree of activity, methods of treatment of JIA in children. Materials and methods. 80 children with JIA were examined. The content of serum cystatin C was determined by enzyme-linked immunosorbent assay. The Hoek formula was used to calculate eGFR based on the level of cystatin C in blood serum. Results. A decrease in eGFR below 90 ml/min/1.73m2 to 63.08 ml/min/1.73m2 based on serum cystatin C was found in 41.3% of children with JIA. The variant of the clinical course of JIA does not affect the concentration of serum cystatin С and the level of eGFR. Meanwhile, a high degree of risk of developing a decrease in eGFR in children with polyarthritis was established - 72.7% versus 48.9% (OR=2.78; CI: 1.07-7.24; p&lt;0.04). Elevated serum cystatin С levels and decreased eGFR are associated with the degree of JIA activity and its duration. A decrease in eGFR is observed in all children with high activity of JIA, 71.4% - with low activity, 28.3% - in remission. A low risk of developing a decrease in eGFR in children in remission of JIA was established - 51.5% versus 91.5% (OR=0.10; CI: 0.03-0.34; p&lt;0.001). The duration of the active stage of JIA ≥4 years negatively affects the level of eGFR, which leads to a high risk of developing a decrease in eGFR - 39.4% versus 17% (OR=3.17; CI: 1.13-8.9; p&lt;0.04). A high risk of developing a decrease in eGFR was established in children with JIA who received non-steroidal anti-inflammatory drugs (NSAIDs) at the time of the examination - 54.5% versus 8.5% (OR=12.9; CI: 3.76-44.25; p&lt;0.001). The use of immunobiological therapy is associated with a low risk of developing a decrease in eGFR - 9.1% versus 46.8% (OR=0.11; CI: 0.03-0.42; p&lt;0.001). Conclusions. Renal dysfunction was found in 41.3% of children with JIA. Its development is affected by high activity of JIA, duration of the active stage of JIA ≥4 years, and treatment with NSAIDs. The study was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the institution specified in the work. Informed consent was obtained from the parents of the children for the research. No conflict of interests was declared by the authors. Key words: juvenile idiopathic arthritis, renal dysfunction.

СЛОЖНОСТИ ДИАГНОСТИКИ ХРОНИЧЕСКОГО НЕБАКТЕРИАЛЬНОГО ОСТЕОМИЕЛИТА У ДЕТЕЙ

The article presents up-to-date data concerning etiopathogenesis, clinical manifestations and diagnosis of chronic non-bacterial osteomyelitis in children. Chronic relapsing multifocal osteomyelitis (CRMO) is a rare condition with unknown etiology, which is characterized by presence of numerous relapsing focuses of bone destruction. Diagnostic work-up for CRMO includes magnetic resonance imaging (MRI) and bone scintigraphy, blood culture and bone biopsy. The diagnosis of CRMO can be made if negative results of blood culture and bone biopsy material are observed and bone malignancy and infection are ruled out. Main therapeutic approaches and follow-up are given in the article. Clinical case of CRMO in combination with juvenile idiopathic arthritis (JIA) in a ten year old boy is described. CRMO should be considered and differential diagnosis should be done in cases of atypical course of JIA especially in those with absence of specific immunological markers.

Infection with SARS-CoV-2 causes flares in patients with juvenile idiopathic arthritis in remission or inactive disease on medication

BackgroundFlares of juvenile idiopathic arthritis (JIA) have been described in the context of various infections. Flares of rheumatic diseases in adults have been described following infection with SARS-CoV-2 in several cohorts. So far, the effect of infection with SARS-CoV-2 on the course of JIA is unknown.MethodsThe database of the German Center for Pediatric and Adolescent Rheumatology was searched for patients with confirmed infection with SARS-CoV-2 and subsequent disease flare, admitted from July 2020 until June 2021. cJADAS-27, ESR and C-reactive protein, as well as uveitis activity, medication at the time of flare and treatment of flare was extracted. Patient cases were described individually.ResultsOut of 988 patients admitted, five patients with remission off medication (n = 2) or inactive disease on medication (n = 3) were identified, with flare symptoms up to four weeks after infection with SARS-CoV-2.ConclusionsFlares can occur after infection with SARS-CoV-2 in patients with JIA in remission or inactive disease on medication. Treating physicians need to be aware of this fact, especially when counseling patients with rheumatic diseases about the respective dangers of COVID-19 and vaccination against SARS-CoV-2.

Прогнозування віддалених наслідків ювенільного ідіопатичного артриту

Актуальність. Ювенільний ідіопатичний артрит (ЮІА) характеризується хронічним запаленням суглобів із прогресуючим перебігом і вираженою тенденцією до ранньої інвалідизації. Тривале спостереження за хворою на ЮІА дитиною дозволяє простежити еволюцію хвороби та оцінити вплив варіанта початку, віку, статі, ступеня активності та інших факторів на перебіг патологічного процесу, що сприятиме прогнозуванню більш чіткого формування несприятливих наслідків хвороби та правильному лікуванню. Метою роботи є удосконалення критеріїв прогнозування суглобової форми ювенільного ідіопатичного артриту (ЮІА) шляхом ретроспективного порівняльного аналізу хворих із тривалістю хвороби 1 рік та 5–7–10 років. Матеріали та методи. Обстежено 47 дітей віком від 2 до 18 років із суглобовою формою ЮІА. Під час уточнення нозологічної форми суглобової патології використовувались клінічні, загальноприйняті лабораторні та інструментальні дослідження. Для розробки прогностичних критеріїв застосовано регресійний аналіз із визначенням інформативності ознак та прогностичних коефіцієнтів для кожної з них. Результати. Установлено, що для прогнозування подальшої 5–7-річної еволюції ЮІА важливе значення мають такі ознаки: стать пацієнтів, наявність ураження дрібних суглобів кистей, наявність ревматоїдного фактора, для 10-річної та довготривалої (понад 10 років) еволюції — наявність уражень очей, кількість як загального числа уражених суглобів, так і числа активних із них. Зростає значущість у прогностичній моделі наявності ревматоїдного фактора, показника тривалості ранкової скутості, рентгенологічної стадії хвороби, лабораторних показників — рівня швидкості осідання еритроцитів, С-реактивного білка. Також для 10-річного прогнозу більше значення має ефективність метотрексату на першому етапі його застосування. Подані моделі визначають варіанти багаторічного перебігу ЮІА: ремісія (до 2 балів), стабілізація патологічного процесу (від 2 до 3 балів) — як сприятливі, а повторні загострення патологічного процесу без прогресування деструктивних змін у суглобах (від 3 до 4 балів), прогресування хвороби із збільшенням рентгенологічних змін у суглобах, що характеризують їх деструкцію (понад 4 бали), — як несприятливі. Висновки. Подані способи прогнозу перебігу ЮІА слід використовувати в перші роки розвитку захворювання, що дозволить вже на цьому етапі еволюції процесу визначити реальну можливість формування несприятливих наслідків та в правильному режимі скоригувати лікування.

AB0732 JUVENILE IDIOPATHIC ARTHRITIS IN ADULTHOOD

Background:Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease of unknown aetiology in childhood. Approximately 40- 60% of patients with juvenile idiopathic arthritis (JIA) have continuous or recurrent disease activity extending into adulthood.Objectives:The aim of this study was to evaluate the clinical, biological and radiological course of JIA in adulthood.Methods:A retrospective study including 35 patients was conducted between 2010 and 2019. The patients enrolled met the ILAR criteria for the diagnosis of JIA. Patients with JIA older than 20 years were included. Data regarding sociodemographic features, Physical growth, disease activity, biological and radiological parameters were analysed.Results:Thirty one patients were recruited. The sex ratio was 0.53. The mean age at the time of the study was 38.9 years [20-69]. The mean age of the disease onset was 9 years [3-16]. These patients were assigned to discrete JIA categories: rheumatoid factor positive polyarthritis (47.7%), rheumatoid factor negative polyarthritis (23.9%), oligoarthritis (14.2%), enthesitis-related arthritis (9.5%), and psoriatic arthritis (4.7%).A failure to thrive was seen in 33.3% of patients. Overweight and obesity were found in 38% and 19% of patients, respectively. Biological inflammatory syndrome was noted in 52% of patients, and 65.2% had active disease. Hip involvement was noted in 43.5% of patients and 17.4% of them had a total hip replacement. Sixteen patients had neck pain and the imagining showed an atloid-axoid dislocation in 50% of them. Radiographs showed a joint destruction in 60.9% of patients and a wrist arthritis was the most frequent involvement.Conclusion:Most of our included patients maintain active disease and have functional impairment in adulthood.Disclosure of Interests:None declared