Variants Of Juvenile Idiopathic Arthritis Research Articles

Application of genetically engineered biopharmaceutical products in children with various JIA forms in the Karaganda region

The article presents the experience of using biopharmaceutical products for the treatment of children with juvenile idiopathic arthritis in the cardio-rheumatological department of the PSE “Children’s Hospital of Karaganda” for the period from January 1, 2013, to December 31, 2017. The study included 46 patients with JIA who were on genetically engineered biological therapy (girls 28-60.8%, boys 18-39.1%). Among all patients, 12 (26.1%) suffered from the oligoarticular variant of juvenile idiopathic arthritis with (JIA), 15 (32.6%) – from polyarticular seronegative variant (JIA), 14 (30.4%) – from systemic form (JIA), and 5 (10.9%) from other variants. Adalimumab was used in 24 patients (50.2%). Tocilizumab in 17 (30%) ones, 14 of which had a systemic variant of JIA. Infliximab was applied for 5 patients (10.8%).

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.

Опыт успешного применения этанерцепта у ребенка с артритом, ассоциированным с энтезитом

Aim: demonstration of a clinical case of the successful use of etanercept in a child with еnthesitis-аssociated аrthritis. Key points. Еnthesitis-аssociated аrthritis is one of the clinical variants of juvenile idiopathic arthritis. The initial therapy of еnthesitis-аssociated аrthritis includes nonsteroidal anti-inflammatory drugs (NSAIDs) and non-biological disease-modifying drugs, the ineffectiveness of which is an indication for the appointment of genetically engineered drugs, in particular, the inhibitor of tumor necrosis factor-α etanercept. Conclusion. Currently, for the treatment of еnthesitis-аssociated аrthritis, if the use of NSAIDs and non-biological disease-modifying drugs is ineffective, genetically engineered drugs should be prescribed, in particular etanercept, which allows to achieve drug remission. Keywords: еnthesitis-аssociated аrthritis, etanercept, children.

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.

Vitamin D Status Among Children With Juvenile Idiopathic Arthritis: A Multicenter Prospective, Non-randomized, Comparative Study.

BackgroundJuvenile idiopathic arthritis (JIA) is a chronic autoimmune disease characterized by destructive and inflammatory damage to the joints. The aim in this study was to compare vitamin D levels between children and adolescents, 1–18 years of age, with juvenile idiopathic arthritis (JIA) and a health control group of peers. We considered effects of endogenous, exogenous, and genetic factors on measured differences in vitamin D levels among children with JIA.MethodsOur findings are based on a study sample of 150 patients with various variants of JIA and 277 healthy children. The blood level of vitamin D was assessed by calcidiol level. The following factors were included in our analysis: age and sex; level of insolation in three regions of country (center, south, north); assessment of dietary intake of vitamin D; effect of prophylactic doses of cholecalciferol; a relationship between the TaqI, FokI, and BsmI polymorphisms of the VDR gene and serum 25(OH)D concentration.ResultsWe identified a high frequency of low vitamin D among children with JIA, prevalence of 66%, with the medial level of vitamin D being within the range of “insufficient” vitamin D. We also show that the dietary intake of vitamin D by children with JIA is well below expected norms, and that prophylactic doses of vitamin D supplementation (cholecalciferol) at a dose of 500–1,000 IU/day and 1,500–2,000 IU/day do not meet the vitamin D needs of children with JIA. Of importance, we show that vitamin D levels among children with JIA are not affected by clinical therapies to manage the disease nor by the present of VDR genetic variants.ConclusionProphylactic administration of cholecalciferol and season of year play a determining role in the development of vitamin D deficiency and insufficiency.

Опыт успешного применения голимумаба у ребенка с ювенильным полиартритом

Objective of the Paper: Demonstration of a clinical case of successful use of golimumab in a child with juvenile polyarthritis. Key points. Juvenile polyarthritis is one of the most disabling clinical variants of juvenile idiopathic arthritis (JIA). In recent years, the range of medicines used in the therapy of JIA has significantly expanded. With the ineffectiveness of methotrexate, the appointment of genetically engineered biological drugs (GIBP) is shown, among which tumor necrosis factor α (TNF-α) inhibitors are most often used, one of which is golimumab. Conclusion. To date, for the treatment of juvenile polyarthritis, there is golimumab in the arsenal of medicines, which is human monoclonal antibodies to TNF-α, which allows to achieve an inactive phase of the disease with the ineffectiveness of the use of other GIBP. Keywords: juvenile polyarthritis, golimumab, children

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.

Association of HLA-G, HLA-E and HLA-B*27 with susceptibility and clinical phenotype of enthesitis related arthritis (ERA)

We studied the association of Enthesitis related arthritis (ERA) the most common variant of juvenile idiopathic arthritis (JIA) in Asians, with HLA-G and -E polymorphisms. HLA-G (14 bp Ins/Del rs371194629, +3142 rs1063320, +3187 rs9380142) and HLA-E (rs1264457, and rs2844724) polymorphisms were analyzed in 127 patients with ERA and 381 ethnically matched healthy controls with TaqMan 5′-nuclease assay using allele-specific fluorogenic oligonucleotide probes. HLA-G and -E polymorphisms were not found to be associated with susceptibility to ERA. HLA-G +3187 (rs9380142) G allele was associated with hip arthritis (Pc = 0.04, OR = 2.22, 95%CI = 1.07–4.63) and hip deformity (Pc = 0.02, OR = 2.51, 95%CI = 1.16–5.43). HLA-B*27 was positive in 91. HLA-E rs1264457 G and rs2844724 T alleles may be associated with B*27 positivity in ERA. Among HLA-G, -E haplotypes, frequency of -InsGAAC was significantly higher in patients than healthy controls (Pc = 0.003). In conclusion, HLA-G and HLA-E haplotype -InsGAAC may be associated with susceptibility to ERA and HLA-G +3187 rs9380142 A>G polymorphism may be a poor prognostic marker for progression to hip arthritis and deformity in ERA-JIA.

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.

Relationship of genetic polymorphism of the acute phase marker of inflammation rs12218 of the SAA1 gene with clinical phenotypes of juvenile idiopathic arthritis

Objective: to test the hypothesis of a possible relationship between the rs12218 polymorphism of the SAA1 gene and a predisposition to different clinical phenotypes of juvenile idiopathic arthritis (JIA).Patients and methods. Genetic typing of rs12218 polymorphism was carried out in 142 children: 77 of them were diagnosed with JIA, including 30 patients with oligoarthritis (oJIA), 20 with polyarthritis (pJIA), and 27 with systemic onset (sJIA). Sixty five healthy volunteers were included in the control group. The rs12218 polymorphism of the SAA1 gene was investigated using real-time polymerase chain reaction.Results and discussion. A high risk of developing the clinical phenotype of oJIA in carriers of the C mutant allele of the rs12218 T/C polymorphism of the SAA1 gene was established. Statistically significant differences between the clinical phenotypes of oJIA and sJIA in the frequency distribution of genotypes and alleles of rs12218 T/C polymorphism of the SAA1 gene are shown.Conclusion. The results of the studies have confirmed the important role of the rs12218 T/C polymorphism of the SAA1 gene in the formation of susceptibility to clinical variants of JIA.

ПОРАЖЕНИЕ ШЕЙНОГО ОТДЕЛА ПОЗВОНОЧНИКА ПРИ ЮВЕНИЛЬНОМ ИДИОПАТИЧЕСКОМ АРТРИТЕ: ЧТО УПУСКАЕТСЯ ИЗ ВИДУ? (СОБСТВЕННЫЙ ОПЫТ И ОБЗОР ЛИТЕРАТУРЫ)

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in childhood, in which involvement of the cervical spine (CS) can lead to clinically significant and irreversible functional impairment. Objective of the study: to provide a comparative characteristic of patients with JIA, depending on the presence of joint arthritis in cervical spine (CS). Materials and methods of the study: the retrospective uncontrolled continuous nonrandomized comparative study included data on patients with JIA (n=753) who were treated at the Clinic from 2007 to 2016. The diagnosis of JIA was diagnosed using ILAR criteria and all children were assessed for articular status. Disorders of the CS were diagnosed on the basis of clinical manifestations, as well as radiation studies. Results: clinical signs of CS injury were detected in 101 patients (13,4%) and were more common in patients with polyarticular (48%, OR=1,8 (1,2; 2,7), p<0,001) and systemic (18 ,9%, OR=3,6 [2,0; 6,6], p<0,001) variants of JIA. A statistically significant relationship has been found between arthritis of the CS and arthritis of the temporomandibular joints (TMJ) (OR=10,4 [5,4; 19,8], p<0,001), glenohumeral joints (OR=14,1 [7,5; 26,3], p<0,001). Patients with CS arthritis had a long disease duration and time to remission, high laboratory inflammatory activity, and the need for more frequent use of systemic glucocorticosteroids. Arthritis of the CS became an independent predictor of the need to use genetically engineered biological drugs (HR=1,78 (95% CI: 1,22; 2,59, p=0,002) and failure to achieve remission (HR=1,33 (95% CI: 1,01; 1,76 (p=0,04): Patients with arthritis of the CS had anterior chronic uveitis less often. Conclusion: all patients with JIA need functional tests to assess the state of the CS even in the absence of complaints. A radiation study of CS should be performed, as far as possible, on all children with polyarticular and systemic variants of JIA, as well as arthritis of TMJ and shoulder joint, unless there are risks of general anesthesia for younger patients.

СLINICAL AND LABORATORY DATA AND ALGORITHM OF MANAGEMENT OF ADULT PATIENTS WITH POLYARTICULAR VARIANT OF JUVENILE IDIOPATHIC ARTHRITIS

Relevance. The polyarticular variant of juvenile idiopathic arthritis (JIA) is a disease that begins in childhood and leads to joint damage and disability in adulthood with significant social losses. At 18, patients go under the supervision of adult rheumatologists, often accompanied by loss of control of the disease due to insufficient compliance from both the patient and the physician. Today, there is no documented process for the transfer of patients from childhood to adulthood in Ukraine. Therefore, creating an algorithm for managing such patients is an urgent task.The polyarticular variant of JIA is a disease that begins in childhood and leads to joint damage and disability in adulthood with significant social losses.
 Objective of this study was to evaluate the clinical and laboratory status and to develop an algorithm for managing adult patients with polyarticular variant of JIA, depending on the detection of RF or/and A-CCP.
 Materials and methods. The study included 168 adult patients from different regions of Ukraine who were diagnosed with JIA in childhood between 1984 and 2014 without severe comorbidities. Inclusion criteria were: 16 to 60 years old; duration of the disease more than 3 years; the presence of documentary evidence of childhood diagnosis of JIA (ambulatory card, hospital records). Among patients with JIA were identified 53 patients with polyarticular variant, of whom 42 or 25% - with RF (-) polyarthritis and 11 or 6.5% - with RF (+) polyarthritis. The disease activity was evaluated by DAS28 and JADAS-10. The questionaries SF-36, HAQ, TAS-20, PHQ-9 were analyzed and remote articular JADI-A and extra-articular JADI-E damages were evaluated. Statistical studies were performed using IBM SPPS Statistics version 25.0.0.0 software, the results were considered to be reliable at 5% critical level (P <0.05). 
 Results. The negative correlation of JADI-A and the patient's physical well-being PCS (r = -0.27, p <0.05) and physical functioning (r = -0.24, p < 0.05), pain intensity (r = -0.24, p <0.05), general health (r = -0.24, p <0.05), vital activity (r = -0, 19, p <0,05), social functioning (r = -0,27, p <0,05), mental health (r = -0,22, p <0,05) according to SF-36. The severity of extra-articular damages JADI-E correlated with PCS (r = -0.22, p <0.05) and physical functioning (r = -0.28, g <0.05), pain intensity (r = -0.20, p <0.05), general health (r = -0.23, p <0.05), and mental health (r = -0.23, p <0.05), but also had a positive rcorrelation with HAM-A (r = 0.25, p <0.05), depression scale (r = 0.28, p <0, 05) and PHQ-9 (r = 0.28, p <0.05). Significantly lower level of physical health was established in patients who requires prosthetics (p <0.001) compared to those who did not need prosthetics. 
 Conclusion. Based on the results obtained, algorithms for managing adult patients with JIA positive for RF or / and A-CCP were developed, depending on the detected articular and extra-articular damages and the need for prosthetics and the psychological status.

Clinical correlates of HLA-B*27 and its subtypes in enthesitis-related arthritis variant of juvenile idiopathic arthritis in south Indian Tamil patients.

The aim of the study was to assess the distribution of human leukocyte antigen (HLA)-B*27 subtypes and its correlation with disease phenotypes in children with enthesitis-related arthritis variant of juvenile idiopathic arthritis (JIA-ERA). One hundred and sixty patients (132 males, 28 females) satisfying the International League Against Rheumatism (ILAR) classification criteria for JIA-ERA were assessed and relevant demographic, clinical and radiographic data were documented. HLA-B*27 typing was done for all the patients and B*27 positive samples were subjected to high-resolution gene sequencing. The effect of duration of illness, HLA-B*27, its subtypes, and gender on the clinical phenotype were analyzed. The mean age of disease onset was 12.69±2.4years with a male:female ratio of 4.7:1.0. HLA-B*27 was positive in 109/160 patients and HLA-B*27:04 was detected in 63% followed by B*27:05 (30%). Duration of illness was greater in patients with skeletal deformity, hip arthritis, sacroiliitis, cervical spine involvement and acute anterior uveitis (AAU) (P<0.05). HLA-B*27 positivity was associated with a prolonged course of disease, higher incidence of AAU (14.7% vs 2%, P=0.015), family history of spondyloarthritis (21.1% vs 5.9%; P=0.015) and higher erythrocyte sedimentation rate as compared to HLA-B*27 negative patients (P<0.01). The HLA-B*27:04 and *27:05 positive patients had similar clinical phenotypes. Presence of HLA-B*27 and long duration of illness results in skeletal deformity, hip arthritis, sacroiliitis, cervical spine involvement and AAU. HLA-B*27:04 followed by B*27:05 are the most common HLA-B*27 subtypes in our study population and both have a similar clinical phenotype.

THE STRUCTURE AND CLINICAL MANIFESTATIONS OF JUVENILE IDIOPATHIC ARTHRITIS IN CHILDREN IN KRASNODAR

Aim. The research was conducted to study the structure (variants, sexual and age characteristics) and manifestations of articular syndrome in children with juvenile idiopathic arthritis in Krasnodar.Materials and methods. There was conducted a retrospective analysis of 89 case histories in patients aged 2-15 diagnosed with juvenile idiopathic arthritis for the first time.Results. As a result of the study, the following variants of juvenile idiopathic arthritis were diagnosed: oligoarticular – in 62 patients (69,6%), polyarticular – in 24 patients (27%) and systemic – in 3 children (3,4%). Group 1 consisted of 62 patients with oligoarticular variant, and group 2 consisted of 24 patients with polyarticular variant. In the sexual aspect, there were 1,5 times more girls than boys among all the studied children. There are also a higher number of the females within the groups. The average age of the onset of the disease in all patients with juvenile idiopathic arthritis was 8,9±0,4 years. In group 1, the average age was 9,6±0,5 years, in group 2 – 7,4±0,4 years. In children with oligoarticular variant of the disease, knee and ankle joints were more often involved in the process. In group 2, the pathological process involved both large joints and small joints of the hands and feet. Leukocytosis, accelerated erythrocyte sedimentation rate and positive results of immunological studies were more often detected among the children of the second group. On the radiographs, cartilage and bone changes were found in 9% of patients.Conclusion. Among the patients with juvenile rheumatoid arthritis, the residents of Krasnodar, the oligoarticular variant dominates (69,7%), the polyarticular RF-negative variant is in second place (25,8%), the systemic variant is in third place (3,4%), and the polyarticular RF-positive variant is in last place (1,1%). In the sexual aspect, there were 1,5 times more girls than boys among all the patients. The onset of the joint syndrome mainly occurs in early school and puberty age. The articular syndrome was manifested mainly by the arthritis of the knee, ankle joints, and the polyarticular variant was also manifested by the arthritis of the wrist joints and small joints of the hands and feet. Among the patients, the signs of humoral activity and immune inflammation were more characteristic of the polyarticular variant. At the onset of disease, the changes of cartilaginous and bony tissues of the joints were identified by the radiography only in 9% of cases.

Remission and Active Disease in Young Adult Patients with Juvenile Idiopathic Arthritis During the Transition Period from Paediatric to Adult Healthcare

The objective of the research was to study the frequency of remission in young adults with juvenile idiopathic arthritis during the transition period from paediatric to adult healthcare and factors contributing to its development. Materials and methods. In our study, there were included 165 adult patients from different regions of Ukraine diagnosed with juvenile idiopathic arthritis according to the classification criteria of the International League of Associations for Rheumatology. All the patients were examined in the Oleksandrivska City Clinical Hospital, Kyiv during 2015-2018. There were assessed the presence of rheumatoid factor, anti-cyclic citrullinated peptide, antinuclear antibodies, human leukocyte antigen B27, disease duration, disease activity (the Juvenile Arthritis Disease Activity Score-10 and the Disease Activity Score-28), C-reactive protein, past medical history, quality of life (the 36-Item Short Form Health Survey), the degree of depression (the Patient Health Questionnaire-9) and alexithymia (the 20-item Toronto Alexithymia Scale). In all the patients, bone mineral density was studied using dual-energy x-ray absorptiometry with the evaluation of T- and Z-scores in different regions of the skeleton. The disease was considered inactive at the Disease Activity Score-28 &lt;2.6 and the Juvenile Arthritis Disease Activity Score-10 &lt;1 and &lt;2 for oligoarticular and polyarticular variants of juvenile idiopathic arthritis, respectively. Results and discussion. All the patients were divided into 2 groups: Group I included 136 (82.4%) patients with active disease at the time of examination; Group II comprised 29 (17.6%) patients who achieved remission according to the Disease Activity Score-28 or the Juvenile Arthritis Disease Activity Score-10. In Group I, females prevailed accounting for 58.1% of patients as compared to Group II (31.0%). Disease duration was longer in patients of Group I (p&lt;0.01); however, they did not differ from patients of Group II in age at disease onset and the International League of Associations for Rheumatology variants of juvenile idiopathic arthritis. In Group II, lesions involving more than 3 joints (p&lt;0.01), hand arthritis (p&lt;0.01), symmetric arthritis (p&lt;0.01), enthesitis (p&lt;0.01), spinal pain (p&lt;0.01) were observed less frequently. Fewer patients required joint replacement (p&lt;0.01); the number of deformed and painful joints (p&lt;0.05, p&lt;0.001, respectively) was smaller. However, there was no difference in the level of rheumatoid factor, anti-cyclic citrullinated peptide, antinuclear antibodies, and the presence of human leukocyte antigen B27. The achievement of remission improved physical well-being of patients (the physical component score, p&lt;0.001), although overall mental well-being (the mental component score) did not change according to the 36-Item Short Form Health Survey. In patients with remission, the indicators of physical functioning (p&lt;0.001), role functioning (p&lt;0.001), social functioning (p&lt;0.001), bodily pain (p&lt;0.001), general health (p&lt;0.001), mental health (p&lt;0.001) improved. There was observed a reduction in the level of depression to the normal one according to the Patient Health Questionnaire-9 (p&lt;0.05); however, in both groups, there were observed elevated levels of alexithymia. Both groups did not differ in the frequency of immunobiological therapy prescription; however, the results should be intepreted with caution, since only 5 (17.1%) patients in Group II received immunobiological therapy earlier or at the time of examination. In Group II, patients did not receive glucocorticoids at the time of examination (p&lt;0.001) and earlier more often (p&lt;0.001). Both groups did not differ in both the duration of treatment with disease-modifying antirheumatic drugs and the doses of methotrexate and sulfasalazine. Conclusions. Remission of juvenile idiopathic arthritis was detected in 17.6% of the surveyed young adult patients from different regions of Ukraine during the transition period from paediatric to adult healthcare, that indicated that in most cases the goal of treat-to-target strategy was not achieved. Patients with active disease often developed joint deformities and required their replacement; they had worse physical well-being according to the 36-Item Short Form Health Survey, although mental well-being was affected in both patients with active disease and those with remission, which may be due to high levels of alexithymia in both groups. Patients with active disease had higher levels of depression according to the Patient Health Questionnaire-9, whereas patients in remission showed no depression.

PROGNOSTIC FACTORS FOR THE RESPONSE TO TOCILIZUMAB THERAPY IN PATIENTS WITH JUVENILE IDIOPATHIC ARTHRITIS WITHOUT SYSTEMIC MANIFESTATIONS: A COHORT STUDY

Background. To assign genetically engineered biologic drugs, we need data on the predictors for response to therapy. Prognostic factors for the response to tocilizumab in patients with juvenile idiopathic arthritis (JIA) without systemic symptoms are poorly studied.Objective. Our aim was to reveal early predictors for the response to tocilizumab therapy in patients with JIA without systemic symptoms.Methods. A retrospective cohort study enrolled patients with JIA without systemic symptoms who received tocilizumab therapy between July 2009 and August 2017. We assessed the association between the initial demographic, clinical, and laboratory parameters in patients and the best response (according to the ACR90 criteria) to treatment after a year.Results. The study included 95 (girls 85%) patients; the mean age was 10.3 (6.0; 13.6). During the first year of therapy, 71 (75%), 55 (58%), 38 (40%), and 22 (23%) patients achieved the improvement according to ACR30/50/70/90 criteria, respectively; 22 (23%) patients reached disease inactive stage according to the Wallace criteria. When performing multivariate analysis, the following improvement predictors were revealed based on the ACR90 criteria after a year of treatment: decrease in serum C-reactive protein level during the first month of therapy [odds ratio (OR) 1.024; 95% confidence interval (CI) 1.007–1.051], decrease in disease activity score on the visual analogue scale according to the parent/patient assessment (OR 1.048; 95% CI 1.005–1.105), early onset of the disease (OR 0.38; 95% CI 0.16–0.72), persistent oligoarthritis according to the ILAR (OR 9.9; 95% CI 1.5–109.3). During the first year of tocilizumab administration, neutropenia was registered in one patient, leukopenia — in three cases, and urticaria — in one case.Conclusion. The variant of JIA, the age at the disease onset, and the disease course pattern in the first month of tocilizumab therapy are the predictors of treatment efficacy throughout the year.

Alexithymia and Quality of Life in Adult Patients with Juvenile Idiopathic Arthritis

Patients with chronic pain disturb not only quality of life (QL) but also develop difficulties in describing their feelings. Prolonged pain, stress, pathological conditions and related emotions can alter the perceived sensation of pain. The aim of our study was to study the QL and the level of alexithymia in adult patients with different types of juvenile idiopathic arthritis (JIA).Materials and methods. 173 young people aged 18-40 years old were examined: 118 adult patients with different ILAR variants of JIA, 30 patients with ankylosing spondylitis (AS) and 25 healthy young people. The QL was assessed using the Short-Form-36 questionnaire (SF36) with further assessing the level of alexithymia by Toronto alexithymia scale (TAS-20).Results. The analysis of QL shows that PCS (44.8±9.9) was significantly lower (p=0.001) in patients with JIA than in healthy subjects (55.7±6.9) of the corresponding age and sex, but did not differ from patients with AS (42.3±7.5). Patients with JIA had lower physical (p=0.001), role functioning (p=0.001) and bodily pain (p=0.001) compared with healthy, with no difference from patients with AS. In the distribution of patients with JIA in groups by the level of alexithymia, differences in QL were not revealed by MCS or PCS and scales related with them. The relationship analysis between the alexithymia and QL in patients with JIA shows, that elevated and high levels of alexithymia were related with low levels of MCS (p&lt;0.05), role functioning (p&lt;0.05), mental health (p&lt;0.05). PCS and physical functioning did not affect the level of alexithymia in adult patients with JIA. PCS, role functioning, bodily pain, and general health were the lowest in patients with poly-articular JIA. However patients with oligo-, poly-articular, enthesyte-related JIA had no differences on scales related to PCS. Patients with poly-JIA with elevated and high levels of alexithymia revealed significantly lower social (p&lt;0.05) and role (p&lt;0.05) functioning, mental health (p&lt;0.05) compared to patients without alexithymia. The presence of low bodily pain in alexithymic patients was found. Signs of alexithymia were found in 90% and 85% of adult patients with the oligo-arthritis and enthesyte-related JIA, respectively. The comparison of the QL in patients with oligo-arthritis and enthesitis-related JIA with different levels of the alexithymia shows no significant differences.Conclusions. 85.2% of adult patients with different variants of JIA have elevated and high levels of alexithymia. Adult patients with JIA have lower physical functioning than healthy individuals of the same age and sex, although they do not differ from the control group and AS group on psychological functioning and related vitality, social and role functioning, and mental health. The presence of alexithymia is related with a low level of psychological functioning, role functioning, mental health. However, physical functioning did not affect the level of alexithymia in adult patients with JIA. Patients with poly-JIA have the lowest physical, role function, bodily pain and general health, but according to the psychological functioning there were no differences between different variants of JIA in adulthood. Patients with poly-JIA with elevated and high levels of alexithymia have significantly lower social (p&lt;0.05), role (p&lt;0.05) functioning and mental health (p&lt;0.05) compared to patients without signs of alexithymia.

FOLLOW-UP OF METHOTREXATE EFFECTIVENESS IN A PATIENT WITH JUVENILE POLYARTHRITIS

научный биометрический журнал, который знакомит читателя с клиническими рекомендациями и особенностями применения лекарственных и вакцинных средств у детей, предоставляет исчерпывающую информацию о воздействии лекарственных средств на плод, о проводимых в

EXPERIENCE IN APPLICATION OF TOCILIZUMAB AT SYSTEM VARIANT OF JUVENILE IDIOPATHIC ARTHRITIS IN THE REPUBLIC OF BASHKORTOSTAN

Background : To summarize the experience in application of tocilizumab at system variant of juvenile idiopathic arthritis in the Republic of Bashkortostan. Patients and methods : In cardiorheumatologic department of Republican Pediatric Clinical Hospital of Ufa there were 9 children (6 boys and 3 girls) aged from 2,5 to 13,8 years (middle age — 8,2 years) under supervision. Middle age in a disease onset made 4,5 years. All patients were exposed to the combined antirheumatic therapy before prescription of tocilizumab. Despite the therapy, the patients still had a high degree of activity of a disease that was the basis for prescription of tocilizumab. The average single dose of a preparation made 11,2 mg/kg for children with body weight under 30 kg, 8,7 mg/kg for children over 30 kg. Results : 8 children were exposed to the continuous therapy with tocilizumab, therapy duration fluctuated from 6 to 52 (on the average 17,8) months. Treatment was stopped at 1 patient because of insufficient effect and at 1 patient because of the development of the undesirable phenomena. The minimum improvement defined as achievement of ACR pedi 30 criterion was reached in all patients throughout the entire period of treatment by the preparation. The prescription of tocilizumab allowed to stop the system manifestations of a disease within 1 month of treatment in all children. The JADAS-27 index decreased twice (from 33,6 to 16,5) in 1 month from the beginning of the therapy. From the 3rd month of treatment all patients showed the normalization of indicators of the peripheral blood characterizing the activity of inflammatory process (ESR, contents of leukocytes and haemoglobin, SRP serumal level). In 3 and 6 months from the therapy beginning 7 patients reached 50%, and 5 and 6 — 70% improvement, respectively. Two children didn't reach 70% improvement in view of remaining insignificant or moderately active articulate syndrome. Conclusion : The analysis of the research results showed high efficiency of tocilizumab concerning system manifestations and activity of inflammatory process. At the same time 3 patients still suffered the moderate articular syndrome in the form of persistent oligoarthritis, 1 patient — in the form of polyarthritis.