Forms Of Juvenile Idiopathic Arthritis Research Articles

E67 Still's disease in children refractory to usual treatments: recourse to biotherapies: challenges and opportunities

Abstract Background Still's disease in children is a rare autoinflammatory disease with distinct characteristics from other forms of Juvenile Idiopathic Arthritis. A better understanding of its mechanism has led to the use of targeted therapies with a significant improvement in patient prognosis. Despite these advances, there are still subtypes of Still's disease refractory to the usual treatments with serious complications. Objective demonstrate therapeutic escalation in the Child’s Still Methods We report the case of a patient unresponsive to multiple disease-modifying antirheumatic drugs (DMARDs), who required high doses of steroids. The biological ones were an inevitable recourse to improve the vital and functional prognosis; with at the end, a therapeutic escape with anti IL1 after two years of favorable response. Case report 12-year-old girl with no particular family history, with Still's disease diagnosed at the age of nine with a typical clinical form: thermal steeple concomitant with a morbiliform and evanescent skin eruption, polyarthritis, with hepatosplenomegaly. The diagnosis was confirmed by a major biological inflammatory syndrome with raise serum ferritin, serum C-reactive protein level and sedimentation rate. Despite doses > 0.5 mg/kg/d of prednisone, she showed high-threshold sensitivity to corticosteroids with the appearance of deleterious effects: Cushingoid obesity, stretch marks and bilateral cataracts. Methotrexate was added at a dose of 12 m/m2/week, without clinical response. She eventually developed severe macrophage activation syndrome which was successfully treated with bolus corticosteroids. Faced with this systemic form refractory to the usual treatments; biotherapy was used. Anakinra was added to his treatment at a dose of 2 mg/kg/day. Impressive improvement in systemic and joint clinical signs occurred within the first few weeks of treatment and acute phase reactants returned to normal. Anakinra was well tolerated and no adverse effects were observed. After 24 months of follow-up and complete clinical remission, without corticosteroid therapy, she presented with a severe flare of her disease with severe inflammatory runaway (SMA) and disseminated intravascular coagulation. After controlling this acute clinical condition with intravenous corticosteroids and ciclosporin; we switched to antiIL6 with a good clinical and biological evolution. Discussion The excellent response to anakinra in this case refractory to conventional treatments suggests that IL1 inhibition could be an important therapeutic target in some patients. Nevertheless, some subtypes of Still's disease escape anakinra after a few years of good response and this has been suggested by some authors. Conclusion Pro-inflammatory cytokines such as interleukin IL1, IL6, and IL18 have been implicated in the pathogenesis of childhood Still's disease. In recent years, targeted biologics have been used with several cases of successful treatment in forms refractory to conventional drugs.

05 Methotrexate improve the foot functional impairment in juvenile idiopathic arthritis

BackgroundFoot involvement in juvenile idiopathic arthritis (JIA) is common and affects about 60% of children [1]. Often overlooked by patients and practitioners, ankle and foot disability has been poorly studied and there are no accepted clinical practice guidelines for the diagnostic approach, as well as for the therapeutic management.ObjectivesOur study aimed to evaluate the effect of medical treatments on functional disability related to foot involvement in JIA.MethodsWe conducted a cross-sectional study including patients with JIA according to the revised ILAR criteria, collected from the rheumatology department of the Kassab National Institute. Sociodemographic and disease data (activity assessed by the Juvenile Arthritis Disease Activity Score 10 (JADAS-10) and therapeutic modalities) were recorded. Ankle and foot involvement were investigated by questioning and physical examination. We used the Oxford ankle foot questionnaire for children (OxAFQ-C); a validated, simple and reproducible score to assess the impact on the quality of life of children with foot problems [2]. This questionnaire encompasses 14 items corresponding to three dimensions: physical, school and play, and emotional. Higher scores represent better functioning. We searched for an association between the different drug treatments for JIA and the OxAFQ-C score.ResultsThe study included 23 patients. The mean age was 13 ± 4 [6–18] years. The sex ratio was 0.42 with a female predominance. The age of the disease was 49 ± 40 months [6–180 months]. The distribution of the different forms of JIA was as follows: oligoarticular (n = 7), enthesitis-related arthritis (n = 6), polyarticular FR + (n = 1), polyarticular FR- (n = 3), psoriatic arthritis (n = 3), systemic (n = 1) and undifferentiated (n = 1). Pain on walking and limitation of the talocrural joint was found in 39% and 30% respectively. The mean JADAS-10 score was 6.72 ± 6.1 [0–20]. Ten patients had high activity. Eighteen patients (78%) were taking level I analgesics and 14 patients (61%) were on non-steroidal anti-inflammatory drugs, 12 of them on demand. Naproxen was the most commonly used drug, followed by diclofenac. Eleven patients (48%) were on a disease-modifying anti-rheumatic drug (csDMARD). Methotrexate (MTX) was prescribed in 30% of cases with a mean dose of 7.91 mg/week [7.5–10]. Only one patient was on sulfasalazine. Four patients (17%) were treated with biologics: Etanercept (n = 3) and Tocilizumab (n = 1). The mean scores of the different domains of (OxAFQ-C) were as follows: 73.52 ± 35.89 [0—100] in the physical domain, 84.2 ± 30 [6.25—100] in the school and play domain, 88.75 ± 24.71 [12.5 – 100] in the emotional domain. There was no statistically significant association between the different domains of the Oxford score and the use of analgesics or NSAIDs (p> 0.05). Similarly, there was no statistically significant association between the different domains of the Oxford score and treatment with biotherapy (p> 0.05). However, patients on MTX had less functional impairment of the feet with a significant improvement in the physical domain (99.26 on MTX vs 62.5 without MTX, p = 0.02, r = 0.6).ConclusionOur work showed that only methotrexate was associated with an improvement in functional foot outcomes in JIA. Further studies are needed to highlight the effect of other therapies, especially biologics.

20 Does hip involvement affect foot and ankle in juvenile idiopathic arthritis?

BackgroundAlthough ankle and foot involvements are common in juvenile idiopathic arthritis (JIA), they are often neglected. Hip involvement, also common in JIA, may affect these joints by creating a chronic imbalance of the musculoskeletal system. However, no studies have been published on this subject.ObjectiveWe aimed to describe ankle and foot impairment in a cohort of patients with JIA and to study the correlation between these impairments and the presence of hip arthritis.MethodsA monocentric cross-sectional study was conducted including JIA patients fulfilling the 2001 ILAR criteria. Patients with congenital malformation of the ankle or foot or with any other foot impairment due to a disease other than JIA were not included. Foot examination was performed on bare feet both in supine and standing position. We completed with an analysis of footprint with a podoscope and shoes examination. Patients were divided in two groups depending on the presence or the absence of hip arthritis on pelvis X-ray, hip ultrasound or hip magnetic resonance imaging.ResultsWe included 35 patients (M/F = 15/20). Hip arthritis was noted in 45.7%. Oligoarticular (43.8%) and enthesitis-related arthritis (25%) were the most frequent form of JIA. Functional complaints related to foot and ankle were reported in 34.3% of cases. The pain was the most frequent symptom (91%), mainly in the hindfoot and ankle (50%). Foot pain was more frequently encountered in the absence of hip arthritis (52%, vs 31.2% in presence of hip arthritis). Physical examination revealed limitation of the talocrural joint in 20% of cases and feet tenosynovitis in 14.3% of cases. Achille tendon enthesitis was found in 8.6% of patients. These abnormalities were more prevalent in the absence of hip arthritis. Half of the patients had hindfoot deviation dominated by hindfoot varus (22.9%). In the group with hip arthritis, a hallux valgus was found in 14.3%, a supraductus of the 2nd toe, and claw toe in one case each. An anomaly of the footprint was noted in 28 patients, including 11 in the group with hip involvement: 7 cases of cavus foot and 4 cases of flat foot. There were no correlations between foot or ankle anomalies with hip impairment apart from an association of flat foot with the absence of coxitis, and a leg length discrepancy more important in the group with hip arthritis.ConclusionsOur study confirms the frequency of foot and ankle involvement as well as hip arthritis during JIA, hence the importance of their systematic screening even in asymptomatic children. Larger-scale studies would be necessary to evaluate with more precision the relation that there could be between hip and foot impairment.

003 Juvenile idiopathic arthritis: a series of 22 cases

Abstract Introduction Juvenile Idiopathic Arthritis (JIA) is a group of conditions in which the first sign of the disease appears before the child's 16th birthday. The common feature is the presence of at least one arthritis of > 6 weeks’ duration with no recognized aetiology. JIA affect approximately one child in 5000 before the age of 16. Materials and Methods This is a retrospective study of 22 cases of juvenile idiopathic arthritis from the department of pediatrics at the Mohammed VI University Hospital in Oujda seen over a period of four years and 7 months (January 2014 to August 2018). Results The patients were 10 girls and 12 boys aged from 1 to 13 years. The hospital frequency of this disease was 0.49%, six clinical forms of onset were seen: 8(36%) had systemic onset JIA, 5(23%) had Oligoarticular JIA, 2(9%) had rheumatoid positive polyarticular JIA, 3(14%) had rheumatoid negative polyarticular JIA, 2(9%) had enthesitis related arthritis, and 2(9%) had undifferentiated arthritis. The diagnosis was based on clinical, biological, radiological and evolutionary elements. The biologic inflammatory syndrome was present in almost all patients in our series. Anti-nuclear antibodies were positive in two cases of polyarticular JIA and rheumatoid factor was positive in 10% of our patients. 25% had radiological features: one patient was classified as Steinbrocker stage I and the second with systemic JIA as stage III. Two other patients with oligoarticular JIA had small joint effusion and fixed flexion deformities. The treatment was with non-steroidal anti-inflammatory drugs, corticosteroids, salicylates and disease modifying anti-rheumatic drugs which were methotrexate in 47% of cases, and biotherapy in 9% of them. Outcome was favorable in most of the patients, but 31% developed complications which were: growth retardation (2), joint deformities (1), and iatrogenic complications of medical treatment (4). The variability of the outcome reflects the extreme heterogeneity of clinical forms of JIA. Conclusion The treatment of a child with JIA cannot be conceived outside of a multidisciplinary pediatric team. The treatment includes medication and measures to maintain a good functional state of the joints, notably rehabilitation and surgery. The biotherapies have revolutionized the therapeutic approach to JIA, with a notable effect of these new molecules, particularly anti TNF, anti-IL 1 and anti-IL 6.

Analysis of chromatin data supports a role for CD14+ monocytes/macrophages in mediating genetic risk for juvenile idiopathic arthritis

IntroductionGenome wide association studies (GWAS) have identified multiple regions that confer genetic risk for the polyarticular/oligoarticular forms of juvenile idiopathic arthritis (JIA). However, genome-wide scans do not identify the cells impacted by genetic polymorphisms on the risk haplotypes or the genes impacted by those variants. We have shown that genetic variants driving JIA risk are likely to affect both innate and adaptive immune functions. We provide additional evidence that JIA risk variants impact innate immunity.Materials and methodsWe queried publicly available H3K4me1/H3K27ac ChIP-seq data in CD14+ monocytes to determine whether the linkage disequilibrium (LD) blocks incorporating the SNPs that tag JIA risk loci showed enrichment for these epigenetic marks. We also queried monocyte/macrophage GROseq data, a functional readout of active enhancers. We defined the topologically associated domains (TADs) encompassing enhancers on the risk haplotypes and identified genes within those TADs expressed in monocytes. We performed ontology analyses of these genes to identify cellular processes that may be impacted by these variants. We also used whole blood RNAseq data from the Genotype-Tissue Expression (GTEx) data base to determine whether SNPs lying within monocyte GROseq peaks influence plausible target genes within the TADs encompassing the JIA risk haplotypes.ResultsThe LD blocks encompassing the JIA genetic risk regions were enriched for H3K4me1/H3K27ac ChIPseq peaks (p=0.00021 and p=0.022) when compared to genome background. Eleven and sixteen JIA were enriched for resting and activated macrophage GROseq peaks, respectively risk regions (p=0.04385 and p=0.00004). We identified 321 expressed genes within the TADs encompassing the JIA haplotypes in human monocytes. Ontological analysis of these genes showed enrichment for multiple immune functions. Finally, we found that SNPs lying within the GROseq peaks are strongly associated with expression levels of plausible target genes in human whole blood.ConclusionsThese findings support the idea that both innate and adaptive immunity are impacted by JIA genetic risk variants.

α2-fraction and haptoglobin as biomarkers for disease activity in oligo- and polyarticular juvenile idiopathic arthritis

ObjectivesUnlike in adult rheumatology, for most forms of juvenile idiopathic arthritis (JIA) no reliable biomarkers currently exist to assess joint and disease activity. However, electrophoresis is frequently found changed in active juvenile arthritis. The objective of this study was to evaluate the α2-fraction of serum electrophoresis and its main components as biomarkers for JIA, categories extended/persistent oligoarthritis and seronegative polyarthritis, in comparison with the conventionally used erythrocyte sedimentation rate and C-reactive protein.MethodsSerum samples and clinical data from 181 patients with JIA were collected. Serum electrophoresis and α2-fraction and its components were determined using standard methods. Relationship between calculated α2-fraction of serum electrophoresis (CA2F) and its components, acute-phase parameters and cJADAS27 was assessed using Pearson’s correlation coefficient and linear regression modelling, adjusting for confounding effects. Results were confirmed in a second cohort with 223 serum samples from 37 patients, using a mixed model to account for repeated measures.ResultsCompared to ESR and CRP, CA2F showed higher correlation to cJADAS27, in particular for persistent oligoarthritis. Of the three components of the α2-fraction, haptoglobin showed the highest correlation to cJADAS27. Regression analysis demonstrated higher ability to predict cJADAS27 for CA2F, and especially for haptoglobin as a component thereof, than for CRP and ESR.ConclusionCompared to conventional methods, α2-fraction of serum electrophoresis and specifically, haptoglobin show higher correlations with disease activity in common subtypes of JIA, representing excellent candidates as biomarkers for disease activity. Further studies are necessary to determine diagnostic value and correlations in other subtypes.

What are the factors associated with the duration of remission of intra-articular corticosteroid injection in juvenile idiopathic arthritis?

Intra-articular corticosteroid injection (IACI) is generally used in the management of juvenile idiopathic arthritis (JIA) to obtain rapid relief of active synovitis and functional recovery and to prevent the need for regular systemic therapy. The aim of this study was to investigate the outcome of IACI treatment and the factors associated with remission of synovitis. The clinical records of JIA patients who received IACI between January 2014 and December 2020 in two pediatric rheumatology centers were reviewed. The procedure was evaluated in terms of efficacy, factors that may affect the duration of remission, procedural and drug-related complications. During the study period, 134 patients received 227 injections and 37 joints were injected more than once. One hundred and six (79%) patients had persistent oligoarticular disease. At the time of injection, all patients were receiving non-steroidal anti-inflammatory drugs, 74 patients were on methotrexate, and 14 patients were on biologics. The median duration of remission without exacerbation of synovitis treated with IACI was 15 (range 1-64) months. The inactivity rate was 81% at the 6th month after the injection. It has been shown that being less than 7years old at disease onset and low initial CRP levels were correlated with a long remission period (p < 0.05). Despite the differences were not statistically significant, the duration of remission was longer in boys, in ANA positives, in HLA-B27 negatives, in patients with concurrent methotrexate treatment and in patients not receiving biologic therapy (p > 0.05). Only two patients (1.5%, 95% CI - 0.6 to 3.5) developed cutaneous hypopigmentation and subcutaneous atrophy as side effects of injection. Intra-articular corticosteroid injection was more effective especially in patients with low initial CRP levels and younger than 7years of age. The duration of remission was longer in these patients. Key Points • Intra-articular corticosteroid injection is an effective method for controlling joint inflammation and achieving long-term remission without significant side effects. • Intra-articular corticosteroid injection can be preferred in all forms of juvenile idiopathic arthritis as primary therapy or to relieve the patient while waiting for the effect of systemic agents or to avoid increasing the dose of systemic drugs. • It can be recommended as a treatment option at any stage of the disease, especially in young patients and patients with low initial CRP values.

Systemic juvenile idiopathic arthritis — current diagnostic and therapeutic management

Juvenile idiopathic arthritis (JIA) is a heterogeneous group of arthritis that has seven subtypes under the currently applicable ILAR classification. It is the most common arthropathy diagnosed in children, a chronic disease affecting children and adolescents. The systemic form of juvenile idiopathic arthritis (SJIA) is the most frequent subtype of the disease with a different aetiopathogenesis, broad clinical picture, various courses, burdened with numerous complications and requiring a therapeutic approach that is different than in other subtypes of JIA. In the case of SJIA, it is essential to establish the correct diagnosis as soon as possible and to initiate effective treatment and, if there is no effect after standard steroid therapy, use targeted anti-cytokine therapy. This review discusses current data on the aetiopathogenesis of the disease, clinical presentation and principles of diagnostic and therapeutic management.

Clinical aspects of HLA-B27 positive enthesitis-related arthritis in childhood

Introduction: Enthesitis-related arthritis (ERA) is a form of juvenile idiopathic arthritis (JIA) according to the International League Against Rheumatism (ILAR) classification. Enthesitis-related arthritis accounts for 8.6 to 18.9% of all children with JIA. The first clinical sign of ERA is usually asymmetrical arthritis of large joints, especially of the lower extremities. Axial involvement is typically presented by unilateral or bilateral sacroiliitis. Enthesopathy is a unique feature of ERA. Aim: The aim of this study is to determine the most common clinical characteristics in children with HLA-B27 positive ERA. Materials and Methods: We performed a retrospective analysis of 55 patients up to 16 years of age, diagnosed with HLA-B27 positive ERA. We used physical and laboratory tests as well as imaging techniques to assess various clinical aspects of ERA in every patient. Results: Demographic characteristics showed prevalence of male gender—44 boys vs. 11 girls (4:1 ratio). The mean age of onset was 13.3 years for boys and 9.9 years for girls. The most commonly affected joints were as follows: knees in 49% of the cases, ankles—in 43.6%, hip joints—in 36.3%, intertarsal/metatarsophalangeal joints—in 20%. Physical examination found enthesitis in 24 of the patients (43.6%). The most commonly affected entheses were: the site of attachment of the Achilles tendon in 66.6% of the cases, the site of attachment of the plantar fascia in 45.8%, the site of attachment of the patellar tendon in 12.5%. Plain X-ray of the sacroiliac joints detected sacroiliitis in 34 of the patients (61.8%). In over 90% of the cases, the sacroiliitis was bilateral. Conclusion: HLA-B27 positive ERA is a rare pathology in childhood. This study confirms typical epidemiological and clinical characteristics of the disease among Bulgarian children.

The Presence of Antinuclear Antibodies (ANAs) in Children with Juvenile Idiopathic Arthritis and Arthritis Related to Infection: a Single Center Experience

Objective - to determine the presence of antinuclear antibodies (ANAs) in children with juvenile idiopathic arthritis (JIA) and arthritis related to infection (ARI). Methods - Retrospective-prospective study at the Clinic for Children’s Diseases Tuzla, from January 2014 to January 2020. Results - 81 children were included in the study: 26 boys and 16 girls with JIA (median age 9.9 years) and 22 boys and 17 girls with ARI (median age 9.6 years). The most common form of JIA was oligoarticular (64.2%), while reactive arthritis (ReA) was the most common form of ARI (64.1%). ANAs were positive in 7/42 (16.6%) children with JIA: 5/27 (18.5%) children with the oligoarticular and 2/10 (20%) children with polyarticular rheuma factor negatve form. Considering ARI, ANAs were positive in 12/39 (30.7%) children: 9 children with ReA (23.1%) and 3 children with postinfectious arthritis (7.6%). We did not find a significant difference in ANAs positivity between the examined groups of children (χ2=1.523; P=0.21). One child with JIA and 25.6% of children with ARI had a positive ANA profile; a statistically significant difference (P=0.002) was found. Conclusion - ANAs tests have little diagnostic utility in clarifying the diagnosis of JIA, and should not be used as a screening tool if JIA is the diagnosis under consideration. The persistence of ANAs was not associated with the type of arthritis, juvenile or ARI.

Evaluation of Patients with Juvenile Idiopathic Arthritis- Associated Uveitis from Rheumatology Perspective

Objective: Uveitis, the most common extra-articular manifestation of juvenile idiopathic arthritis (JIA), is most commonly found in children with oligoarticular type and polyarticular rheumatoid factor (-) JIA. Close follow-up of these children by pediatric rheumatologists and ophthalmologists is important because of the risk of blindness if these cases are untreated. This study aims to evaluate the frequency of uveitis, demographic characteristics, and complications in children with JIA. Material and Methods: Among the patients with JIA who were followed up at the Pediatric Rheumatology Clinic of Dr Sami Ulus Maternity, Child Health and Diseases Training and Research Hospital between January 2017 and July 2021, those with uveitis were included in the study. Location of uveitis, laterality, age at onset of uveitis, complications of uveitis, duration of follow up, laboratory findings, medications used, and status of uveitis at the time of data collection were obtained from the patients’ files. Results : Uveitis was observed in 34 (7.1%) of the 473 children with JIA included in the present study. Twenty three patients were female (67.6%). The age at diagnosis of JIA was 5.9±5.1 years, and the age at diagnosis of uveitis was 7.5±4.2 years. The most common form of JIA was the persistent oligoarticular form. Compared with the age of onset of arthritis in all JIA patients, the age of onset of arthritis was lower in patients with JIA-associated uveitis (7.8±4.6 years vs. 5.9±5.1 years). Anatomically, all patients had anterior uveitis. Antinuclear antibody positivity was more common in children with JIA-associated uveitis (47.1%) than all of our patients with JIA (19%). In one of the patients, arthritis and uveitis were diagnosed simultaneously. Posterior synechia was found in three patients (8.8%). Arthritis was the first symptom in 27 patients (79.4%) and uveitis in six patients (17.6%), cataract in five patients (14.7%), glaucoma in two patients (5.9%), and blindness in one eye (2.9%). Conclusion: Uveitis is the most common extra-articular complication of JIA and has sight-threatening complications which may lead to irreversible visual loss. The findings of this study suggest that the joint effort of pediatric rheumatologists and ophthalmologists is needed to diagnose these children promptly and treat them appropriately. Key Words: Eye diseases, Juvenile Idiopathic Arthritis, Uveitis

Assessment of the trophological status of children with rheumatic diseases

Background. Analyzing modern medical literature, it can be noted that in pediatric rheumatology, insufficient attention is paid to assessing the trophological status of sick children. Purpose: to investigate the nutritional status of children with various nosological forms of rheumatic diseases (RD). Materials and methods. The nutritional status of 35 children with RD was investigated, of which 5 patients had systemic variant of juvenile idiopathic arthritis (JIA), 13 patients had articular form of JIA, 4 patients had systemic lupus erythematosus, 3 patients had mixed connective tissue disease (Sharp’s syndrome), 6 children had juvenile systemic scleroderma, 4 patients had juvenile dermatomyositis. All patients underwent a generally accepted comprehensive clinical, laboratory and instrumental examination. To assess the trophological status, the body mass index and the blood serum leptin were determined by the enzyme immunoassay and the trophological status coefficient was calculated. Results. The results of the conducted studies indicate that trophological insufficiency of varying degrees manifested in 78.5 % of children with RD in a decrease in body weight, depletion of muscle mass, adipose tissue, changes in the skin and its appendages, mucous membranes, organs of vision, oral cavity, cardiovascular system. The most pronounced trophological insufficiency was found in children with systemic JIA, with juvenile scleroderma and dermatomyositis.

ОЦЕНКА ЭФФЕКТИВНОСТИ И БЕЗОПАСНОСТИ ПРИМЕНЕНИЯ ЭТАНЕРЦЕПТА У ПАЦИЕНТОВ С НЕСИСТЕМНЫМИ ВАРИАНТАМИ ЮВЕНИЛЬНОГО АРТРИТА: 10-ЛЕТНИЙ ОПЫТ ПРИМЕНЕНИЯ В УСЛОВИЯХ ФЕДЕРАЛЬНОГО ЦЕНТРА

TNF-α inhibitors are used in the treatment of non-systemic variants of juvenile idiopathic arthritis (JIA) in case of ineffectiveness or intolerance to methotrexate. Despite 20 years of experience of using of etanercept in pediatric rheumatology, a long-term study of the efficacy and safety of the drug in real clinical practice remains necessary. Objective of the study: to study the efficacy and safety of etanercept for treatment of various non-systemic JIA subtypes in real clinical practice. Materials and methods of research: data from the case histories of 375 patients (242 girls and 133 boys) with articular forms of JIA for 2010–2020 were included in a retrospective, open, uncontrolled, nonrandomized, continuous multicenter cohort study. The age of debut was 6.3 (2.9; 10.7) years. Demographic characteristics, subtypes of arthritis, indicators of laboratory activity of inflammation, and outcomes were estimated: achievement of remission, exacerbation, and switching from etanercept to another genetically engineered biological drug (GEBD) were assessed. Results: remission was recorded in 78.9% on average after 6 months. The factors that determine the likelihood of achieving remission were the absence of previous therapy with GEBD (p=0.001) and compliance with therapy – OR=2.5 (95% CI: 1.3; 4.7), p=0.006. Exacerbations were recorded in 29.5% and were associated with the presence of the HLA B27 antigen – OR=2.6 (95% CI: 1.1; 6.0), p=0.028, antinuclear factor seropositivity (p=0.060). Change of etanercept to another GEBD was made in 17.4% of children and was associated with a failure to achieve remission – OR=7.7 (95% CI: 4.0–14.3), p=0.000001, with previous exacerbations – OR=14,8 (5.3; 41.2), p=0.0000001 and the development of de novo uveitis – OR=2.4 (95% CI: 1.1–5.3), p=0.038. The arthritis subtype and the presence of concomitant methotrexate therapy did not significantly affect treatment outcomes. Conclusion: achievement of remission, compliance with therapy, history of previous therapy with GEBD, exacerbation of JIA and development of de novo uveitis determined the main outcomes of etanercept therapy. The JIA subtype, as well as concomitant therapy with methotrexate, did not significantly affect the outcomes of the disease, which makes it possible to consider etanercept therapy a very effective and safe method of treating JIA as a genetically engineered first-line therapy of any variants of articular forms of JIA, even in monotherapy with ineffectiveness or intolerance to methotrexate.

Evaluation of pediatric patients with јuvenile idiopathic arthritis treated with biological therapy Tocilizumab (Actemra)

Juvenile idiopathic arthritis (JIA) is the most common chronic disease in childhood. It manifests a heterogenic group of symptoms of arthritis, lasting at least 6 weeks and it appears before the age of 16. Patients who had no good therapeutic response to conventional therapy with Methotrexate were treated with biological therapy. The aim of this paper was to evaluate 9 patients who were receiving Tocilizumab at the Department of Rheumocardiology, University Clinic of Pediatric Diseases in Skopje. Materials and methods: Our study included 9 patients treated at our Department with biological therapy with Tocilizumab. Prior to initiation of the biological therapy, all patients underwent laboratory investigations, purified protein derivative (PPD) skin test for tuberculosis, X ray of the lungs and heart, and analysis of hepatitis markers. All patients were treated with amp. Actemra (tocilizumab) 8 mg/kg/tt i.v. Two of the patients had a severe form of the disease (one with severe systemic form and one with severe oligoarticular form of JIA). All presented patients had clinical remission of the disease. Conclusion: Therapy with tocilizumab in patients with juvenile idiopathic arthritis is a good therapeutic choice. The results obtained in our study have shown a significant therapeutic effect of tocilizumab even in severe forms of the disease.&#x0D;

P010 Clinico-epidemiological characteristics and outcomes of Juvenile Idiopathic Arthritis (JIA) patients in Kenya: data from the KAPRI registry

Abstract Background Pediatric rheumatic diseases pose a significant disease burden upon children and their families (1–3). They lead to physical disability and diminished quality of life (1–3). Determination of the burden and clinical characteristics of these diseases is a critical first step to improving access to care and optimizing use of existing health systems for the well-being of these patients (4). This is in line with the goal of the Bone and Joint decade (2000–2010) aimed at increasing recognition and understanding of the impact of musculoskeletal diseases (5,6). The Kenya Pediatric Rheumatology Registry (KAPRI) offers a unique opportunity to pioneer and spearhead a systematic and organized format to inform policy and better healthcare provision. Our objective was to determine the patient characteristics, clinical features and outcomes of Juvenile Idiopathic Arthritis (JIA) patients assessed at the Aga Khan University Medical College East Africa from March 2019 to December 2020. Methods Data of JIA patients on age, gender, laboratory and clinical features at diagnosis and treatment options offered were extracted from the database. A further detailed chart review was undertaken to determine the proportion of patients who achieved remission or minimally active diseases. Results Among the 207 patients enrolled thus far, 16 (7.7%) were diagnosed to have JIA. Majority of the patients were females (75%; n = 12) with a mean age of 7 years and 3 months (Range : 1 year—13 years 7 months). All patients had joint pain and swelling as the initial presenting complaints. Majority of the patients had polyarticular JIA (75%, n = 12). The other 4 patients were oligoarticular (n = 2) and systemic JIA (n = 2). Among the polyarticular JIA patients (n = 12), only 3 (25%) were rheumatoid factor (RF) positive and 1 was antinuclear antibody (ANA) positive. The oligoarticular and systemic JIA patients were all negative for antinuclear antibody, rheumatoid factor and cyclic citrullinated peptide antibodies (anti-ccp). Seven patients (43.8%) required biological therapies; tocilizumab (n = 2: systemic JIA), adalimumab (n = 2: polyarticular JIA), etanercept (n = 2: polyarticular JIA) andtofacitnib (n = 1: polyarticular JIA). One patient with systemic JIA on tocilizumab developed herpes simplex which was successfully managed with oral acyclovir. All the other patients did not develop any infections, allergic reactions or any other untoward events as adverse outcomes following the use of biological therapies. Five patients have attained remission as illustrated in the table below. Two patients have been lost to follow up. Conclusion Seronegative polyarticular JIA was the predominant form of JIA observed with a predilection to affect more girls and boys. Over a period of 2 years, remission has been attained among 31.25% of the patients (5 of 16) with use of synthetic disease modifying anti-rheumatic drugs and biological therapies.

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.

The importance of lower extremity involvement type on exercise performances, function, and quality of life in peripheral predominant forms of juvenile idiopathic arthritis

BackgroundJuvenile idiopathic arthritis (JIA) can cause reduced exercise capacity, deterioration in functional activities, and poor health-related quality of life. This study aims to objectively reveal lower extremity involvement in the peripheral predominant forms of juvenile idiopathic arthritis through qualitative evaluations and to determine the effects of these involvements on exercise, function, and quality of life.MethodsThirty-two patients with a history of peripheral arthritis and aged between 7 and 16 years participated in the study. Demographics, JIA subtype, disease duration, arthritis and deformities of the lower extremity, disease activity score, 6-min walk test (6MWT), cycling exercise test (CYC-E), childhood health assessment questionnaire (CHAQ), and pediatric quality of life inventory (PedsQoL) scores were recorded. In case of clinical suspicion of arthritis, an ultrasonographic examination was performed for a definitive diagnosis. Regression analyses were performed to explore the most associated lower extremity involvement and patient characteristics for each of the dependent variables including 6MWT, CYC-E, CHAQ, and PedsQoL.ResultsOf the total number of patients, with a mean age of 12.91 (SD 2.37) years, 28.1% had knee arthritis, 15.6% foot arthritis, 12.5% hip arthritis, and 37.5% lower extremity deformity. The parameters that were most associated with CHAQ and PedsQoL were hip and knee arthritis, whereas CYC-E was found to be most associated with knee arthritis and height, and 6MWT was found to be most associated with hip arthritis, knee arthritis, and demographic characteristics.ConclusionThis study emphasizes the importance of hip and knee arthritis, which are among the determinants of walking endurance, function, and quality of life; and knee arthritis, which is among the determinants of cycling performance in JIA with lower extremity involvement.

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.

The Increased Levels of Fecal Calprotectin in Children With Active Enthesitis Related Arthritis and MRI Signs of Sacroiliitis: The Results of a Single Center Cross-Sectional Exploratory Study in Juvenile Idiopathic Arthritis Patients.

Enthesitis related arthritis (ERA) is a specific subtype of juvenile idiopathic arthritis (JIA), often regarded as an undifferentiated form of juvenile spondyloarthritis (jSpA). While gut is increasingly recognized as origin and/or target of inflammation in adult onset spondyloarthritis (SpA), the incidence of gut involvement in ERA patients is largely unknown. The aim of this study was to measure the concentration of fecal calprotectin (fCAL), a surrogate marker of gut inflammation, in patients with different subtypes of JIA, as well as to correlate the results with various demographic, clinical, laboratory, imaging, and treatment characteristics. The cross-sectional exploratory study involving 71 patients with ERA, other forms of JIA and children complaining musculoskeletal symptoms was therefore conducted. Along with fCAL assessment, a detailed clinical and laboratory examination was performed, including the calculation of a composite disease activity scores. Moreover, MRI of the sacroiliac joints was performed in all ERA and other patients complaining of low back pain. The median concentration of fCAL was highest in ERA patients (33.2 mg/kg, p = 0.02), with a significant difference between those with inactive and active disease (20.0 vs. 57.4, p = 0.01), as well as those with and without MRI signs of sacroiliitis (22.6 vs. 54.3, p = 0.04). The fCAL did not differ depending on the NSAID use (23 vs. 20, p = 0.18), although weak correlation was observed with the treatment duration (r = 0.25, p = 0.03). In conclusion, our findings indicate that a parallel inflammation in musculoskeletal system and gut can occur not just in adults with SpA, but in children with ERA as well.

Prevalence and significance of serum 14\u20133-3\u03b7 in juvenile idiopathic arthritis

BackgroundPrompt diagnosis of juvenile idiopathic arthritis (JIA) is important to avoid long term complications. Elevated serum 14–3-3η levels improve the diagnostic sensitivity of rheumatoid factor (RF) and cyclic citrullinated peptide (CCP) antibody in adult rheumatoid arthritis (RA), and have been associated with more severe phenotype. We investigated the prevalence and clinical significance of serum 14–3-3η in different types of JIA.MethodsJIA patients (n = 151) followed by the Pediatric Rheumatology Core at Children’s Hospital of Los Angeles were categorized into 5 groups: polyarticular JIA RF+ (PJIA RF+; n = 39), PJIA RF- (n = 39), psoriatic arthritis (PsA; n = 19), enthesitis-related arthritis (ERA; n = 18), and oligoarticular JIA (OJIA [control group]; n = 36). RF, CCP antibody, and 14–3-3η were measured for all patients. 14–3-3η serum levels > 0.2 ng/mL were considered positive. Disease activity was assessed by the Juvenile Arthritis Disease Activity Score-71 (JADAS-71).ResultsElevated 14–3-3η levels were detected in 34/151 (23%) patients, and across all groups tested. Most patients with 14–3-3η had titers ≥4 times above the cutoff value. The majority (22, 65%) of 14–3-3η-positive patients were also positive for RF or CCP antibodies, 16 (47%) were positive for all 3, and 12 (35%) were single-positive for 14–3-3η. The highest prevalence of 14–3-3η was in PJIA RF+ patients (49%), followed by OJIA (22%). Positivity for 14–3-3η was not significantly associated with disease activity or age at diagnosis.ConclusionSerum 14–3-3η can be detected in all forms of JIA tested but appears to be most common in PJIA RF+. 14–3-3η does not appear to correlate with disease activity in JIA.