This review summarizes the international experience of pneumococcal immunization of patients with juvenile idiopathic arthritis (JIA). The high efficiency and safety of pneumococcal vaccines in children with JIA is shown. Numerous studies have demonstrated an adequate immune response after vaccination even during therapy with immunosuppressive and genetically engineered biological agents drugs. Prevention of the pneumococcal infection helps avoid the development of pneumonia in patients with JIA.

The article presents the follow-up of a patient with severe systemic juvenile idiopathic arthritis (JIA) resistant to glucocorticosteroids, to the first genetically engineered biologic drug (GEBD) tocilizumab, a monoclonal antibody to the interleukin (IL) 6 receptor. Switching to the second GEBD — a monoclonal antibody to IL1β canakinumab — provided a remission of the disease. The first injection of the drug fully arrested the systemic symptoms of the disease, and the fourth one — the articular syndrome. The presented clinical example shows that switching to GEBD with a different mechanism of action — a monoclonal antibody to IL1β canakinumab — is highly effective and induces a remission of the disease in patients with systemic JIA resistant to tocilizumab. There were no adverse events under pressure of canakinumab therapy.

The article describes the international experience in monitoring of patients with juvenile idiopathic arthritis. The main goal of most existing international registers of children with juvenile idiopathic arthritis is to evaluate various aspects of the effectiveness and safetyof genetic engineering biological drugs in comparison with methotrexate. No results from the analysis of the effectiveness of registers as a tool for long-term monitoring of the disease and medical care for children with systemic juvenile idiopathic arthritis have beenfound in the available literature.

Objective: Our aim was to study features of the drug therapy of children with systemic juvenile idiopathic arthritis (sJIA).Methods: We conducted a retrospective data analysis included in the Register of sJIA cases, for the period from 2002 to 2015.Results: The indicators of 384 children with sJIA are studied. Prior to the diagnosis verification, all patients were prescribed to intake antipyretic agents, 98% — antibiotics. After the diagnosis, non-steroidal anti-inflammatory drugs (NSAIDs) were intaken by 282 (73.4%) patients: diclofenac sodium — by 163 (40.1%), nimesulide — by 88 (22.9%) patients. The average duration of NSAID intake from 2002 to 2015 decreased from 81.5 ± 115.3 to 3.3 ± 3.7 months (p < 0.001). Prior to the diagnosis verification, glucocorticoids were received intravenously or intramuscularly by 265 (69.0%) patients, orally — 176 (45.8%). Totally, glucocorticoids were received by 330 (85.9%) patients: methylprednisolone — 300 of 384 (78.1%), prednisolone — 174 (45.3%), there were totally 1855 prescriptions in 668 patients. The average duration of glucocorticoid intake from 2002 to 2015 decreased from 13.7 ± 26.7 to 5.0 ± 3,8 months (p < 0.001). As a disease-modifying drug, methotrexate was intaken by 237 (61.7%), Cyclosporin — by 193 (50.6%) patients. There were totally 809 prescriptions of genetically engineered biological preparations (GIBP) in 430 patients: in 2002–2005–8, in 2011–2015–602 in 397 patients (p = 0.001). Tocilizumab is intaken by 210 (52.9%) of 397 patients, kanakinumab — 37 (9.3%) patients. The disease duration from the manifestation to the prescription of immunosuppressive drugs from 2002 to 2015 decreased from 27.3 ± 23.9 to 1.0 ± 0 months (p < 0.001), GIBP prescriptions — from 70.7 ± 26.3 to 0.5 ± 0.7 months, respectively (p < 0.001).Conclusion: In 13 years there have been positive changes in the antirheumatic therapy in children with sJIA — the duration of NSAIDs and glucocorticoids intake reduced, the period between diagnosis verification and immunosuppressants and GIBP prescription decreased. However, it is still widely used antibiotics, non-selective NSAIDs and glucocorticoids.

The article presents an observation of one of the most common autoinflammatory syndromes — TRAPS (periodic syndrome associated with a mutation in the TNF α receptor gene). During a molecular-genetic examination of a 9-year-old child, a c.337_339del deletion in the heterozygous state of the TNFRSF1A gene exon 04, leading to a p.Glu113del amino acid deletion, was found. This mutation has not been described previously in TRAPS patients, and according to computer analysis (Alamut Visual) the issue is pathogenic. This observation indicates the presence of families with TRAPS in the Russian population, who can have «atypical» TNFRSF1A gene mutations. A successful use of monoclonal antibodies to interleukin 1 — canakinumab — in the patient is described. As a result, fever and abdominal syndromes have completely stopped, while knee joints pain decreased a day later. After a week of treatment, the child’s disease activity laboratory indices returned to normal (ESR, C-reactive protein). No exacerbations were fixed over the next 32 weeks. No adverse effects were registered during canakinumab therapy. Thus, canakinumab has demonstrated a high level of effectiveness and safety for the patient suffering from a periodic syndrome associated with a mutation in the TNF α gene receptor. This indicates therapeutic use prospects for the interleukin 1 β blocker in TRAPS syndrome patients.

The article shows the observation of rare NLPC4-associated autoinflammatory syndrome with enterocolitis and familial cold urticaria. Diagnosis is confirmed molecularly-genetically: previously not described mutation c.928C>T in the heterozygous state in NLRC4 gene is discovered by a method of the new generation sequencing. The use of a monoclonal antibody to the interleukin 1 canakinumab provided complete relief of fever and skin and intestinal symptoms in just 1 week of treatment. Later the signs of inflammation have disappeared completely; the patient’s quality of life improved and life-threatening complications were prevented. The above example demonstrates the high clinical efficacy of canakinumab in the patient with NLRC4-associated autoinflammatory syndrome and suggests promising therapeutic use of interleukin 1 blockers in such patients. There were no adverse events during canakinumab therapy.

Actuality: The complexity of the diagnosis of abdominal forms of periodic disease often leads to unnecessary surgical intervention. Objective: To evaluate the characteristics of the course of periodic disease in children, and to develop patient management algorithm during an exacerbation. Materials and Methods: The presented analysis of treatment of 18 patients with Barrett’s esophagus. We describe the medical history, the clinical picture of the disease, laboratory and instrumental examination of patients, including genetic testing; and also carried out a detailed differential diagnosis with other acute surgical diseases. Conclusions: Adherence to the algorithm of diagnosis of periodic disease to avoid unjustified surgical interventions

Background. Osteoporosis — a typical manifestation of systemic juvenile idiopathic arthritis (JIA) and aggravation of glucocorticosteroid therapy. High risk of fractures with osteoporosis remains an urgent issue of rheumatology. Objective: Our aim was to study the effect of tocilizumab on bone tissue with patients having systemic JIA. Methods. History of children’s disease (< 18 years) with systemic JIA and known results of densitometry of the lumbar spine (L1–L4) before and after 12 months of tocilizumab therapy have been studied. Results. Anamnesis of 49 patients (including 24 girls) having systemic JIA have been analyzed. The median age of patients was 14 (7; 21), the age of onset of the disease — 4 (1; 14), disease duration — 9 (2; 19) years. High activity of the disease has been noted with all chlidren; 23 (47%) had limitation of functional activity (score on the questionnaire CHAQ). 36 (74%) children took 0.5 mg/kg of glucocorticosteroids per day orally, 32 (65%) — intravenously. Tocilizumab was applied for all children in a dose of 12 mg/kg 1 time every 2 weeks. Prior to prescribing tocilizumab, osteoporosis (Z-score <-2.5 SD) was detected with 15 (30%) children, osteopenia (Z-score -1 and -2) — with 14 (29%) children, past bone fractures — with 5 (11%) children. After 1 year of treatment, inactive stage of the disease/remission according to the criteria of C. Wallace was recorded with 100% of patients; physical activity (assessed by CHAQ) increased. Glucocorticosteroids per os dose was decreased to 0.05 mg/kg per day for all patients; pulse therapy was not performed. Along with the therapy, increase in the values of Z-score from baseline -1.2 (-5.8; 1.9) to -0.7 (-4.7, 3.0) after 12 months of therapy (p <0.001) and mineral bone density — 0.6 (0.3, 1.3) 0.7 (0.4, 1.2) respectively (p <0.001) was observed. New bone fractures were not observed. Conclusion. Therapy that included tocilizumab resulted in positive changes in bone status with patients having systemic JIA.

Actuality: The complexity of the diagnosis of abdominal forms of periodic disease often leads to unnecessary surgical intervention. Objective: To evaluate the characteristics of the course of periodic disease in children, and to develop patient management algorithm during an exacerbation. Materials and Methods: The presented analysis of treatment of 18 patients with Barrett’s esophagus. We describe the medical history, the clinical picture of the disease, laboratory and instrumental examination of patients, including genetic testing; and also carried out a detailed differential diagnosis with other acute surgical diseases. Conclusions: Adherence to the algorithm of diagnosis of periodic disease to avoid unjustified surgical interventions

This article describes a case of successfully used tocilizumab (interleukin 6 receptors monoclonal antibodies) in a two-year patient with severe systemic juvenile idiopathic arthritis resistant to oral and parenteral glucocorticoids, nonsteroidal anti-inflammatory drugs, and methotrexate. Just after the first injection of tocilizumab, fever and pain ceased, morning stiffness decreased significantly; laboratory disease activity indices normalized by the 4th week of drug use; by the 16th week inflammatory changes in the joints regressed completely, the disease entered its inactive phase. After using tocilizumab, remission duration was 20 months for articular syndrome and systemic manifestations. No adverse reactions have been registered.

Objective: Our aim was to study demographic and clinical characteristics of patients with systemic juvenile idiopathic arthritis (sJIA), timing of diagnosis and routing of the children after the onset of the disease according to the All-Russian Register of the Union of Pediatricians of Russia.Methods: Retrospective study (1998–2015) analyzing indicators from 384 children with sJIA.Results: The majority of patients live in the Central and Volga Federal Districts — 157 (40.9%) and 68 (17.7%) patients, respectively. The ratio of girls to boys is 1.25:1; 281 (73.2%) children got sick under the age of 5. In 35 (9.1%) children the disease is hereditary. The trigger factor in 1/3 of patients was an infection. At the onset of the disease, fever was recorded in all patients, rash — in 190 (49.5%), enlargement of the liver and/or spleen — in 150 (39.1%), and serositis — in 56 (14.6%) patients. 17 (4.4%) children had 5 manifestations of systemic disease, 117 (30.5%) — 4, 64 (16.7%) — 3, 73 (19.0%) and 73 (19.0%) — 2 and 1. 175 (45.6%) children had arthritis at the onset of the disease and extra-articular manifestations were observed for 6 months. 7 (1.8%) patients were hospitalized to the specialized rheumatology departments, 50 (13.0%) — to the cardiologic departments, and 190 (49.5%) — to the pediatric departments. 250 (65.1%) patients were diagnosed with an infectious disease. None of the patients was diagnosed with sJIA within first 6 weeks. The average duration of the disease from the onset to diagnosis was 2.0 ± 15.5 (0–139) months, from the onset to the admission to a special department of the federal research center — 8.0 ± 29.3 (0–146) months, from diagnosis to the admission to the federal research center — 3.0 ± 28.0 (0–138) months; 50 (13.1%) patients were hospitalized without a diagnosis (established at the federal research center).Conclusion: According to the All-Russian Register, sJIA is characterized by aggressive beginning at an early age with severe extra-articular manifestations and late addition of the articular syndrome. In most cases, the verification of diagnosis and admission of patients to the specialized rheumatology departments of the federal research center were carried out in later periods.

The article describes a case of polyarticular juvenile idiopathic arthritis lesions of the cervical spine. This clinical example demonstrates the high efficiency of tocilizumab in a patient with polyarticular juvenile idiopathic arthritis with lesions of the cervical spine. After the first injection of tocilizumab a decrease in the following was observed: pain in the cervical spine and affected joints, severity of functional disorders in the temporomandibular joint and the interphalangeal joints, cervical spine; a 30% improvement in the JADAS, ACRpedi30 was achieved. By the 8th week of therapy the proliferative changes in the joints of the hands and arthralgia decreased, as well as the duration of morning stiffness. After 3 months there was a decrease in the activity of Jia (DAS28), and the erythrocyte sedimentation rate and serum concentrations of C-reactive protein. Adverse effects during therapy with tocilizumab were not observed. The disease activity decreased, (assessed using the visual analog scale (VAS)), as well as the functional impairment (assessed using the Children Health Assessment Questionnaire (CHAQ)). The emotional status and quality of life of the child and her family improved significantly.

Objective: Our aim was to study the prevalence and clinical features of autoinflammatory syndromes among patients with systemic juvenile idiopathic arthritis. Methods: A prospective nonrandomized study was conducted. All its members have been studied for mutations in TNFRSF1A and NLRP3 genes by the sequencing method. Results: 90 children (27 boys, 63 girls) aged from 1 to 17 (average age 8.2) years, with a guide diagnosis: «Systemic juvenile idiopathic arthritis», were examined. As a result, 10 (14%) patients showed mutations in TNFRSF1A gene, leading to the development of TRAPS-syndrome (8 had the most common mutation of R92Q; 3 — not previously described mutations in NLRP3 gene). 2 patients had the diagnosis of CINCA/NOMID Syndrome, 1 — Muckle–Wells Syndrome. In three cases, mutations leading to the development of TRAPS-syndromethe were identified in the first line of descent. Classical examples of autoinflammatory syndromes such as cryopyrin-associated periodic syndrome (CAPS), and tumor necrosis factor receptor associated periodic syndrome (TRAPS). The data about their pathogenesis, clinical features, diagnosis and treatment is presented. Conclusion: It is shown that early detection and adequate treatment of patients with autoinflammatory syndromes, characterized by severe disease and serious prognosis, is difficult due to lack of awareness of pediatricians and unavailability of genetic diagnosis of these syndromes. The necessity of the development of a universal model of the diagnostic algorithm for identification of autoinflammatory syndromes using next-generation sequencing technologies is grounded.

Background: Treatment of patients with juvenile idiopathic arthritis (JIA) is one of the most complex and urgent problems of rheumatology.Objective: Our aim was to evaluate the efficacy and safety of adalimumab therapy combined with immunosuppressants in patients with JIA without systemic manifestations.Methods: A monocentre observational comparative study was held. We studied the results of treatment of patients with JIA being treated with adalimumab combined with immunosuppressants (n = 215) and methotrexate (n = 200). The efficacy of the therapy was evaluated using the paediatric criteria of the American College of Rheumatology (ACRpedi) and remission criteria by C. Wallace during 5 years.Results: After 6 and 12 months the remission of articular syndrome was registered in 72 and 81% of patients treated with adalimumab combined with immunosuppressants, and in 53 and 65% treated with methotrexate. Laboratory indicators of the disease activity corresponded to the reference values after 6 months in 73 and 48%, after 12 months — in 94 and 68% of patients in the comparison groups, respectively. After 6 and 12 months of supervision the activity according to the CHAQ questionnaire was fully recovered in 63 and 79%; 47 and 62% of children. After 1 month the improvement according to the ACRpedi30/50/70 criteria was registered in 87/54/25% of the observed treated with adalimumab. After 6 months the ACRpedi30/50/70 index was 93/89/76% and 63/57/47% for adalimumab therapy with immunosuppressants and methotrexate, respectively. Adalimumab combined with immunosuppressants more quickly than methotrexate induced the stage of inactive disease/remission — after 5 (3; 8) and 12 (6; 18) months, respectively (p < 0.001). After 6 and 12 months of supervision the stage of inactive disease/remission was reported in 43 and 47% of patients treated with adalimumab combined with immunosuppressants, and in 9 and 38% of patients receiving the methotrexate therapy. Adalimumab and methotrexate were well tolerated by 58 and 73% of patients with JIA without systemic manifestations. The adverse events were reported in 42 and 27% of patients, but became the reason for drug dechallenge only in 6 and 10% of patients.Conclusion: Adalimumab combination therapy combined with immunosuppressants has faster and more evident anti-inflammatory effect than the treatment with classical immunosuppressant methotrexate.

The article presents a case report of an early debut and severe clinical course of juvenile rheumatoid arthritis with eyes’ lesion. Authors describe successful administration of human monoclonal antibodies to tumor necrotizing factor (TNF) — adalimumab. In 2 weeks of treatment the morning joint stiffness was stopped, in 4 weeks exudative alterations in affected joints were vanished, and the range of their motions increased. Results of laboratory tests: ESR and concentration of C-reactive protein in plasma were normalized in 6 weeks. Adalimumab initiated development of remission of bilateral uveitis in 8 weeks. Key words: children, juvenile rheumatoid arthritis, rheumatoid uveitis, adalimumab, treatment. ( Voprosy sovremennoi pediatrii — Current Pediatrics. – 2010;9(3): 140-146 )

Represented here is a case of early juvenile idiopathic arthritis associated with uveitis diagnosed in a three-year-old female patient subject to treatment with the standard methotrexate dosage. At the initial stage of treatment, the child demonstrated severe articular syndrome, inflammatory reactions affecting eyeball surfaces, increased laboratory indicators of the illness and functional insufficiency. Successful overcoming of methotrexate resistance through dosage increased up to 20 mg/m2 of body surface per week was described. Over three months of subcutaneous methotrexate treatment with a 15 mg/m2-per-week dose, the child showed milder joint exudation an, arthralgia, less lengthy morning stiffness, although there was no 50% improvement based on ACRpedi criteria, and uveitis was first recognized in the subactive phase. The dose was increased up to 20 mg/m2 per week. By the eighth week of methotrexate treatment, uveal inflammation reversed. Non-active phase and remission were detected in 6 and 12 months respectively. The remission has persisted for 6 years. No side effects have been observed throughout methotrexate treatment.

Treatment of juvenile idiopathic arthritis (JIA) is one of the most complex and urgent problems of rheumatology. Objective: We undertook a study to evaluate the effectiveness and safety of long-term therapy with etanercept in patients with JIA without systemic manifestations. Methods and patients: Patients in the study were divided into 2 groups. Patients of the main group (n = 197) received etanercept, the comparison group (n = 200) - methotrexate. The effectiveness was assessed by the American College of Rheumatology (ACR) criteria and Wallace's criteria for clinical remission (CR) and the 4-year JADAS71 index. Results: We included 397 patients with JIA. In 6 months and 12 months a remission of articular syndrome was detected in 72 and 53 patients respectively; 83% and 65% of patients receiving etanercert and methotrexate, respectively. Laboratory indicators of disease activity corresponded with reference values in 91 and 48% in a period of 6 months, in 12 months - in 94 and 68% of patients. According to the results of Childhood Health Assessment Questionnaire (CHAQ) functional activity fully recovered in 65 and 79%; 30 and 58% of children in a period of 6 and 12 months of follow-up. Within 1 month improvement according to ACR pedi criteria 30/50/70 was achieved in 79/62/34% of patients treated by genetically engineered biological agents. After 6 months AKRpedi criteria 30/50/70 was achieved in 97/96/89% and 63/57/47% against the background of therapy with etanercept and methotrexate, respectively. Etanercept induced inactive stage of the disease / remission [6 (4, 9) and 12 (6, 18) months; p <0,0001, respectively] in significantly shorter time than methotrexate. Within 6 and 12 months of follow up inactive stage of the disease / remission was reported in 30 and 49% of patients treated with inhibitor etanercept, and 9 and 38% of patients receiving methotrexate. Disease activity index JADAS71 in children treated with etanercept was significantly lower than in patients treated with methotrexate for 1 year. Conclusion: Etanercept has a significantly faster and more pronounced anti-inflammatory effect than the classic immunosuppressant methotrexate.

Background: At present, it is urgent to find ways to overcome the inefficiency of and intolerance to the methotrexate therapy in patients with juvenile idiopathic arthritis (JIA). A promising method is the use of TNF-alpha inhibitors as monotherapy.Objective: Our aim was to evaluate the efficacy and safety of etanercept monotherapy and treatment with etanercept and methotrexate in patients with JIA without systemic manifestations.Methods: Observational study with retrospective assessment of the treatment of patients who received etanercept — the treatment group (n = 55) and the combination of etanercept and methotrexate — the control group (n = 136). The efficacy was evaluated for 3 years using the pediatric criteria of the American College of Rheumatology (ACR), remission criteria by C. Wallace and index JADAS71.Results: Total amount of patients with JIA without systemic manifestations under study is 191. As early as 1 month after the first etanercept injection, clinical and laboratory parameters of disease activity significantly decreased in 83 and 77% and functional ability of joints improved in 87 and 74% of patients treated with TNF- inhibitor and its combination with methotrexate. After 6 months, the improvement according to the ACR pediatric criteria 30/50/70 was recorded in 98/98/96 and 96/95/86%; inactive stage of the disease/remission was recorded in 44 and 24% of patients who received etanercept and etanercept + methotrexate. After 1 year, the improvement was recorded in 100 and 100/98/93% of patients in the treatment group and the control group and inactive stage of the disease/remission — in 65 and 43% of patients. In the course of etanercept + methotrexate therapy, infectious adverse events were more common. 12.7 and 7.3% of patients treated with etanercept and methotrexate discontinued their participation in the study during the first 6 months and 18 and 10% — during the first year. 8.4% of patients treated with the combination of etanercept and methotrexate discontinued their participation in the study during the second year.Conclusion: Etanercept monotherapy is effective on a par with the combination therapy, but it has a higher safety profile and a lower therapy «survival».