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In order to study the effect of anxiety and depression on the severity of chronic pain syndrome, 216 patients with the diagnosis of juvenile idiopathic arthritis (JIA) were examined. All children included in the study underwent a traditional rheumatological examination, with an assessment of the disease activity, and a psychometric assessment of the severity of pain, anxiety and depression. Comparison of various clinical groups showed significantly higher levels of severity of anxiety and depression in the case of chronic pain syndrome regardless of the presence of active or inactive phase of JIA, which confirms the necessity of using evidence-based psychological interventions such as relaxation techniques and cognitive behavioral therapy in all patients with JIA suffering from pain.

Objective: to study the efficiency and safety of tocilizumab (TCZ) therapy in patients with systemic-onset juvenile idiopathic arthritis (sJIA). Patients and methods. The retrospective study included 48 children with active sJIA in whom TCZ therapy was initiated because of the inefficiency of using different anti-rheumatic drugs. The investigators studied the time course of changes in the main indicators of sJOA activity, as well as the possibility of achieving remission in accordance with the Wallace criteria (2004). Results and discussion. The main demographic characteristics of the study group (median [25th and 75th percentiles]) included the age of the patients (9.9 [5.0; 12.7] years) and the duration of TCZ therapy (27.0 [5.9; 89.7] months). 40 (83.3%) patients achieved remission; the median of its achievement was 138.5 [56.0; 255.0] days. The patients who had achieved remission had milder sJOA: hepatosplenomegaly, pulmonary and cardiac involvements, and macrophage activation syndrome were less frequently observed. At baseline, they also had higher hemoglobin values and a lower erythrocyte sedimentation rate, and decreased levels of leukocytes, granulocytes, C-reactive protein (CRP), lactate dehydrogenase (LDH) and ferritin. The main predictors for achieving remission, which were estimated using the analysis of sensitivity and specificity, as well as Cox regression models, were CRP ≤82.0 mg/l (OR – 7.9; HR – 1.17); ESR ≤32 mm/h (OR – 17.0; HR – 0.85), ferritin ≤273 ng/ml (OR – 56.5; HR – 2.6), hemoglobin >113 g/l (OR – 17.0; HR – 1.33), LDH ≤676 U/l (OR – 113.6; HR – 3.2), platelets >335⋅109 /l (OR – 5.0; HR – 2.5), and a decline in white blood cells two weeks after the first infusion by more than 11% (OR – 13.0; HR – 6.0) and in granulocytes by more than 12% (OR – 14.0; HR – 4.7). Conclusion. Children with a less severe course of sJIA more promptly reached remission during TCZ therapy. Male gender, high inflammatory activity, previous glucocorticoid therapy, long time to achieve remission, and TCZ dosing regimen deviations were the main factors for an exacerbation of sJOA. Male sex, signs of the high disease activity, preceding CS treatment, long time to achievement of inactive disease and treatment protocol deviations increased risk of sJIA flare.

Kawasaki disease (KD) is acute systemic vasculitis of unknown etiology. Approximately 20–25% of untreated patients develop coronary artery changes with a range of severity from asymptomatic coronary artery dilatation to giant coronary artery aneurysms with thrombosis, myocardial infarction, and sudden death. To date there is no official data on the incidence of KD in Russia. In Russia, the disease is not enough known now to a wide circle of physicians and often masks other more common diseases. Since 2010, the detection rate of KD has dramatically increased in Saint-Petersburg.Objective: to analyze the experience in diagnosing and treating KD in two largest hospitals of Saint Petersburg.Patients and methods. The retrospective study included data on 30 children (18 boys, 12 girls) who were hospitalized with a diagnosis of KD in the Saint-Petersburg State Pediatric Medical University Clinic and Children’s Hospital One (Saint Petersburg) between January 2011 and September 2016. Data are represented by median and extreme values. The age of the children was 2.8 (0.2; 4.6) years; of them 5 (16.7%) patients were under the age of 1 year. The children were hospitalized on 5 (1; 14) days of disease onset; KD was diagnosed on 9 (3; 52) day of the disease.Results. Immediately after diagnosis, 27 (90%) children received aspirin. In early stages (before 10 days of the disease), intravenous immunoglobulin (IVIG) therapy was performed in 15 (50%) children, one of them received IVIG before disease day 5 (on day 3), but without effect. On disease days 11-20 (immediately after diagnosis), 10 (33.3%) children were prescribed with IVIG; thereafter fever was abolished in all the patients. Their body temperature became normal on day 11 (6; 23). Ultrasonography revealed coronary artery lesions in 13 (43.3%) patients. Out of the 30 children followed up, one baby who fell ill at the age of 3 months and received IVIG died on day 30 of the disease.Conclusion. Currently, there continues to be a delayed diagnosis of KD. IVIG therapy was effective, especially in cases of timely diagnosis. It is necessary to increase awareness of KD among clinicians and ultrasound diagnosticians.

Autoinflammatory diseases (AIDs) are a group of rare disorders characterized by persistent or recurrent inflammation caused by the hyperactivation of mediators and innate immune cells (neutrophils, monocytes/macrophages). The paper describes the authors' own case of NLRP12-associated AIDs and the efficiency of canakinumab therapy and reviews a series of cases of the similar disease, which are given in the literature.

Background: Juvenile idiopathic arthritis (JIA) associated uveitis may be the cause of not only visual acuity decrement, but also blindness. At the same time, in some patients therapy with methotrexate can not prevent the development of these complications.Objective: Our aim was to investigate the efficiency and safety of using a tumor necrosis factor inhibitor (adalimumab) in patients with JIA-associated uveitis.Methods: We conducted a retrospective single-arm study of a series of cases. The results of using adalimumab were evaluated in patients with JIA-associated chronic anterior uveitis, who have been under observation for no less than 1 year before and after starting using adalimumab. The latter was prescribed due to progressing and/or recidivous methotrexate-resistant uveitis.Results: We have analyzed clinical case records of 36 children with JIA-associated uveitis. At the start of therapy with adalimumab, actual uveitis was diagnosed in 30 (83%) patients. Remission was achieved in 29 of 30 cases in 2 (2; 12) weeks in patients with actual uveitis. 11 (31%) patients had a uveitis exacerbation 28 (13; 69) weeks after adalimumab therapy started. Adalimumab reduced the exacerbation frequency from 4 (1; 9) to 0 (0; 1) exacerbations per year for one patient (p < 0,001), and reduced the proportion of patients who were treated with topical glucocorticosteroids (from 83 to 8%). There were no differences (in achieving remission and reducing exacerbation frequency) with regard to patients’ sex, involvement of one or both eyes in the disease onset, antinuclear factor seropositiveness, uveitis type and character of joints affection.Conclusion: Adalimumab promotes fast and long-lasting remission of JIA-associated methotrexate-resistant uveitis.

Many orphan diseases in children require life-long and regular intravenous enzyme replacement therapy. The article describes the first Russian practice of implanting venous port systems in 12 patients with type I and II mucopolysaccharidosis and Pompe disease (6 months to 17 years old) to create long-term venous access. Currently, implantable venous port systems are used in 9 (75%) of 12 patients. 4 cases of thrombosis are observed in 3 patients. All of them have been successfully treated. 1 patient had a rotation of the port camera with a membrane facing downwards due to violation of an implantation technique. The camera was adjusted during the second operation.

Background: Uveitis is one of the most common extra-articular manifestations of juvenile idiopathic arthritis (JIA). Currently, the possibility of reducing the risk of uveitis in children with JIA by using methotrexate has been studied.Objective: Our aim was to analyze the results of treatment of children with JIA by studying the relation between the use of methotrexate and the risk of uveitis.Methods: A retrospective uncontrolled study. The case histories of patients with JIA who were treated for at least 2 years after the onset of the disease were studied. The results of treatment of patients who received and who did not receive methotrexate were studied (standard therapy — non-steroidal anti-inflammatory drugs and intra-articular injections of glucocorticoids). The established cases of uveitis were taken into account.Results: The study analyzed the results of observation of 281 children with JIA. In the methotrexate group, uveitis was detected in 22/191 (11.5%), and in the control group — in 42/90 (46.7%) of patients (OR 6.7; 95% CI 3.7–12.3). The time period between the onset of JIA and development of uveitis in two groups under study was the same and equal to 24 (12; 67) and 17 months (7; 35), respectively (p = 0.232). Multivariate regression analysis showed that the main predictors of uveitis were oligoarticular course of JIA (HR = 1.89), positive antinuclear antibody test (HR = 2.14), onset of JIA under the age of 5 (HR = 2.56), female gender (HR = 1.82),and the absence of methotrexate in the therapy (HR = 0.24).Conclusion: The treatment with methotrexate may reduce the risk of uveitis in patients with JIA. To confirm this hypothesis, randomized studies are needed.

Pachydermodactyly is a rare form of fibromatosis, which is characterized by an asymptomatic soft tissue enlargement around the proximal interphalangeal (PIP) joints of the hand. The etiology of the disease is unknown. Its possible triggers are recurrent minimal trauma, a habit or compulsive need to intertwine or rub the fingers. Spindle-shaped finger deformation with soft tissue thickening around the PIP joints mimics the clinical presentation of juvenile idiopathic arthritis (JIA). The distinctive features may be the absence of morning stiffness, contractures, pain, inflammatory and immunological changes in blood tests; however, it is the opinion of a number of authors that pachydermodactyly can be correctly diagnosed only after morphological examination. The paper gives the clinical manifestations of the disease and approaches to its diagnosis and differential diagnosis. It also describes the results of a retrospective study of 5 patients diagnosed as having pachydermodactyly. The final diagnosis was established after laboratory, instrumental, and morphological studies. Specific therapy has not been elaborated; however, by taking into account possible precipitating factors, excessive trauma of the affected finger bone should be avoided. The timely recognition of the disease allow to avoid administration of aggressive antirheumatic therapy required for JIA.

Macrophage activation syndrome (MAS) is a severe life-threatening complication presenting with hemophagocytosis, pancytopenia, coagulopathy, and liver and CNS dysfunctions. The disease belongs to a group of histiocytic disorders. The common triggers for MAS are rheumatic diseases, particularly systemic juvenile idiopathic arthritis (SJIA), infectious diseases, immunodeficiency, and medication. The paper describes the main stages of the pathogenesis of MAS and the role of hypercytokinemia. It presents the clinical picture of MAS and hemophagocytic lymphohistiocytoses. The evolution of diagnostic approaches to diagnosing MAS and related conditions, such as hereditary and secondary hemophagocytic lymphohistiocytosis, is considered. It is shown that it is important to elaborate diagnostic criteria for patients with SJIA. Main current approaches to therapy for MAS are outlined.

Farber disease (lipogranulomatosis, OMIM 228000) — is extremely rare autosomal-recessive disorder from group of lysosomal storage disorders, due to deficiency of acid ceramidase activity enzyme. Farber disease has a lot of clinical masques and resembles to different inflammatory disorders, such as juvenile arthritis, chronic urticaria, larynx papillomatosis and others. Most effective therapeutic method is bone marrow transplantation, which leads to minimization of disabling and improve quality of life. Currently a medication for enzyme replacement therapy of Farber disease is produced and it is under the clinical trials. We describe clinical course of two patients with different types of Farber disease. First case — 10 years old boy with II–III type of disease, and second — with fatal outcome in the age of 4 years 3 months of boy with I (classical) type of Farber disease.

Mucopolysaccharidosis is the group of hereditary metabolic disorders; it is characterized by accumulation of glycosaminoglycans owing to storage of specific lysosomal enzymes. Background: Research objective was to study the influence of enzyme replacement therapy on a somatic state and psychomotor development of children with mucopolysaccharidosis type I and II of various severity in dynamics and to estimate its efficiency. Patients and methods: The data of five years' supervision over 13 patients with mucopolysaccharidosis type I and II is used in the research. During the work the therapy efficiency analysis is made by the following criteria: data of objective examinations, ultrasound investigation of liver, spleen and heart, quantitative determination of excretion of urine glycosaminoglycans, assessment of articular and abarticular affection by JADI scale, assessment of social age and social coefficient by Doll's scale. Results: The reliable distinctions in the contents of urine glycosaminoglycans and also by results of an objective assessment of the liver and spleen sizes and of ultrasonic research of the spleen area in 6 and 12 months of treatment in comparison with basic data are received. The reliable decrease in social coefficient indicator at the first stage of therapy is registered, and then distinctions have insignificant character. There was no essential dynamics of the articular status on treatment that is connected with process stabilization. There are no reliable evidences of both positive and negative dynamics on myocardium involvement, ultrasonic characteristics of the sizes of hepatic lobes. Conclusion: Enzyme replacement therapy is an effective method of treatment of somatic manifestations of various types of mucopolysaccharidosis.

29 children with monoarthiritis were included in our study. Besides routine clinical and laboratorial examination, knee arthroscopy with synovial biopsy was performed in all patients. Visual examination of synovial hyperplasia and hyperemia and microscopic examination was performed. Patients were divided into 2 groups with primary and secondary (associated with joint traumatic damage) synovitis. Patients with primary synovitis had significantly lower disease onset age, lower hemoglobin level and higher ESR and CRP and disease duration compare with secondary synovitis group. Intensive and very intensive type of synovial hyperplasia more frequently in first group, in second group more frequently mild and moderate type of synovial hyperplasia occurred. Correlation between synovial hyperplasia and hyperemia has been revealed (r=0,72, p

Aim: to perform retrospective evaluation of tocilizumab (TCZ) treatment every 2 and 4 weeks. Patients and methods: 33 children with systemic juvenile idiopathic arthritis (sJIA) were observed. Results: children, who need TCZ treatment every 2 weeks had more severe sJIA course. Patients which were treated every 4 weeks had higher TCZ efficacy, no new cases of macrophage activation syndrome (MAS), lower frequency of organ involvement and relapses during TCZ treatment. In 5 (20,8%) children of this group the TCZ-free remission was achieved, and in 3/5 children total drug-free remission lasted the maximum 1085 days was reached. Only 1 children in 4 weeks group developed relapse which leaded to re-start of TCZ treatment with the same efficacy as at first. No patients, who were treated every 2 weeks experienced TCZ-free remission. Also 4 cases of MAS were detected in children who had MAS before the start of TCZ. In 3/4 TCZ was discontinued but in 1 MAS TCZ accompanied with corticosteroids was prolonged. No new MAS cases were detected during this study. Infusion reactions lead to TCZ discontinuation were in 9,1%. 1 death (3,0%) during the trial. Conclusions: we offered the set of clinical and laboratorial criteria of high and low risk patients who need TCZ treatment every 2 and 4 weeks consequently.Key words: systemic juvenile idiopathic arthritis, interleukine-6, tocilizumab.

Autoinflammatory syndromes (AISs) are a group of predominantly hereditary diseases associated with the spontaneous uncontrolled production of proinflammatory cytokines. Most diseases are known to have molecular mechanisms and an inheritance pattern. The paper describes major AISs, such as familial Mediterranean fever; cryopyrin-associated periodic syndrome (familial cold urticaria, Muckle – Wells syndrome, CINCA/NOMID syndrome); tumor necrosis factor-α receptor-associated periodic syndrome; hyperimmunoglobulinemia D syndrome; periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis syndrome. An inheritance pattern and molecular defects are characterized for each disease. The principles of diagnosis and therapy are described. The role of interleukin-1 blockers in the therapy of AIS is defined. The most important symptoms that can be used to detect the major forms of AIS are identified. The Gaslini score, a special formula using the clinical symptoms to identify patients at high risk for AIS who need genetic typing and those at low risk for AIS, is described. A clinical diagnostic algorithm is presented, which can be used to detect patients with AIS and to determine indications to and the time of molecular genetic typing, and to choose priority genes.