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Systemic corticosteroids are continued to be administered in juvenile idiopathic arthritis (JIA) patients, especially in systemic JIA (sJIA), despite the ability of biologic therapy. One of the complications of long-term CS treatment is delayed hip arthritis development with risk of secondary hip osteoarthritis formation and total hip arthroplasty (THA).We compared different types of hip joint lesions in JIA, especially, secondary hip osteoarthritis development and THA rates in systemic and non-systemic JIA, and evaluate systemic corticosteroids contribution to those complications.The study included 753 JIA patients. They were divided into 2 groups: patients with sJIA and non-systemic JIA (nsJIA). Clinical and demographic characteristics, CS treatment regimens were compared.Results. Hip arthritis was found equally often in both groups, but both secondary hip osteoarthritis (19% vs 5,3%) and THA (8.6% vs 1.6%) prevailed in the sJIA. Patients with sJIA had delayed hip involvement (57.9% vs 30.6%; p=0.019), earlier secondary hip osteoarthritis development (4.5 vs 5.1 years after the JIA onset) with younger age of secondary hip osteoarthritis achievement (13.7 vs 15.2 years; р=0.045), they also had higher inflammatory activity, greater systemic corticosteroids administration (94.8% vs 56.1%; р=0.0000001) and higher cumulative systemic corticosteroids dose (3085 mg vs 2000 mg; p=0,005). More than half patients (56.1%) with nsJIA had systemic corticosteroids treatment and impaired calcium-phosphorus metabolism.Conclusion. Systemic corticosteroid treatment and delayed hip involvement are independent predictors of secondary hip osteoarthritis in all JIA categories. Calcium and phosphate metabolism disturbances are additional predictor for secondary hip osteoarthritis in non-systemic JIA categories

Introduction. In children with rheumatic diseases, severe fungal infections (invasive mycoses – IM) are not well understood.Objectives. To analyze risk factors, disease course of IM in children with systemic rheumatic diseases.Materials and methods. For diagnosis of IM were used criteria EORTC/MSGERC, 2019. We reviewed the literature over the past 15 years on IM in children with rheumatic diseases from the international databases Pubmed and Web of Science.Results. In retrospective multicenter study were included 8 children with IM and systemic rheumatic diseases: ANCA-associated vasculitis (n=4), systemic lupus erythematosus (n=3), juvenile rheumatoid arthritis (n=1). Median age was 13,5 (8-17) y., boys – 67%. Invasive aspergillosis was diagnosed in 5 patients and invasive candidiasis – 3. The risk factors of invasive mycoses were high rheumatic disease activity (100%), corticosteroids (prednisolone ≥ 0,3 mg/kg/d) use for ≥21 d (87,5%), immunosuppressive therapy (87,5%), recent (≤ 2 weeks) pulse steroid therapy (75%), hemophagocytic lymphohistiocytosis (62,5%), prolonged (≥ 10 days) severe neutropenia (≤ 0,5х109/l) (62,5%), and prolonged (≥10 days lymphopenia (≤ 1,0х109/l) (37,5%). In patients with invasive aspergillosis the involved organ was the lung, in patients with invasive candidiasis a candidemia was diagnoses. All patients received antifungal therapy. The overall 30 days survival rate was 37,5%.Сonclusions. Children with high rheumatic diseases activity and intensive treatment with immunosuppressive agents should be considered as patients with a high risk of invasive mycoses with a high mortality.

In the article the case of parvovirus B19 infection in a child, which occurred in the form of carditis and myositis, was presented for the first time. There was the rapid progression of the symptoms of acute rhabdomyolysis with a sharp increase in blood levels of creatine phosphokinase, lactate dehydrogenase, myoglobin, ferritin and troponin 1. Ultrasound examination revealed diffuse inflammatory changes in the muscles of the upper and lower extremities with multiple foci of disorganization of the muscular tissue. A high level of PVB19 DNA was determined by the quantitative PCR method, which allowed verifying the parvoviral B19 infection. Rapid clinical and laboratory response in the observed patient was the result of adequate complex therapy, including due to the early use of drugs with antiviral and immunomodulating action.

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.

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.

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.