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Juvenile idiopathic arthritis (JIA) is a multifactorial immune-mediated inflammatory disease in childhood, the most common type of rheumatic disease in children. It is characterized by the polygenic type of hereditary predisposition.Objective: to study the association of STAT4 rs7574865 G/T and IRF5 rs2004640 G/T polymorphisms with the predisposition to certain JIA subtypes in the Russian pediatric population.Patients and methods. The investigation enrolled 177 patients, including 66 patients diagnosed with JIA and 111 healthy unrelated volunteers (a control group). Of the 66 patients with JIA there were 30 (45%) with oligoarthritis: 20 (67%) with human leukocyte antigen B27(HLA-B27)-positive JIA (that was associated with enthesitis, HLA-B27 positive JIA (JIA-B27), 10 (33%) with anterior uveitis concurrent with antinuclear antibody-positive JIA (JIA-uveitis); 20 (30%) with polyarticular JIA (JIA-poly), seronegative for rheumatoid factor; and 16 (24%) with systemic JIA (JIA-sys). As a control for genotyping STAT4 rs7574865 G/T and IRF5 rs2004640 G/T polymorphisms, the investigators studied 103 and 111 DNA samples from healthy adult volunteers, respectively. STAT4 rs7574865 G/T and IRF5 rs2004640 G/T polymorphisms were investigated using allele-specific real-time polymerase chain reaction (RT-PCR).Results and discussion. In the oligoarticular JIA group, the frequency of the STAT4 T allele was significantly higher than that in the control group (38.3 and 20.4%, respectively; p=0.004). This allele was also significantly more common in the JIA-B27 (35.0 and 20.4%, respectively; p=0.044) and JIA-uveitis (45.0 and 20.4%, respectively; p=0.021) groups compared with the control one. No significant differences were found in the frequency of the mutant STAT4 T allele between the control group and the JIA-sys and JIA-poly groups. Regression analysis showed that the identification of the STAT4 T allele was associated with the high risk of a predisposition to oligoarticular JIA as a whole (odds ratio, OR 2.43; 95% confidence interval (CI) 1.23–4.70; p=0.007), as well as to the antinuclear antibody-positive oligoarticular JIA with uveitis (JIA-uveitis): the risk in T allele carriers was 3.2 times higher than that in the control (OR 3.19; 95% CI 1.09–9.06; p= ). A high risk for predisposition was also found in the JIA-B27 subgroup compared with the control (OR 2.10; 95% CI 0.38–4.60; p=0.070). There were no statistical differences in the frequency of genotypes and alleles of the IRF5 rs2004640 G/T polymorphism between the entire group of JIA as a whole and its individual clinical types, as well as the control group.Conclusion. This pilot study confirmed that the STAT4 rs7574865 G/T polymorphism was associated with the risk of oligoarticular JIA, mainly that of JIA-uveitis and JIA-B27.

BackgroundBiological therapy in patients with pediatric rheumatology disease may be associated with adverse events up to demyelinative lesion of CNS including multiple sclerosis (MS). It is a rare condition in the pediatric practice.Objectivesto describe the clinical case of newly diagnosed psoriasis and subsequently developing of multiple sclerosis in pediatric patient revealed in JIA who has been followed-up in Pediatric department of V.A. Nasonova Research Institute of Rheumatology for 8 years.MethodsDescription of clinical case of 13 y.o. male Caucasian pts presented with polyarthritis variant of juvenile idiopathic arthritis (JIA) since 2006.ResultsThe first symptoms (at the age of 1,5) were polyarthritis with fever, morning stiffness and inflammatory activity in laboratory tests in chronological link of DTP – re-vaccination. The patient admitted to the regional hospital where JIA was diagnosed and he received traditional therapy including NSAIDS, methotrexate, numerous of intraarticular injections, methylprednisolone pulse therapy with initial response. By the 2012 the child deteriorated with progressive polyarthritis, deformation of wrist joints, bilateral camptodactylia with progressive destruction on X-ray. Under the administration of abatacept therapy in our clinic in 2012 the significant improvement (70-90% ACR response) was achieved. 2 years later the plaque psoriasis developed. The cutaneous changes were impaired by the regular local application of GC so infusions of abatacept were continued. In 4th years of regular therapy (in the age of 13) sudden neurological symptoms such as headache, loss of sensitivity, ataxia, visual field defect appeared. He was admitted to neurological clinic. Multiple sclerosis was diagnosed based on the presenting signs and symptoms supporting cranial MRI – multiple focal areas of demyelination.ConclusionWe presented a patient with JIA who developed two different immunological related adverse events under long-term abatacept using: psoriasis “de novo” appeared as a native origin of juvenile arthritis and CNS – multiple sclerosis. This is the first case of developing MS under the abatacept therapy among the 1118 pts (2002-2018) who receive biological therapy in our clinic.Disclosure of InterestsNone declared

BackgroundFibrodysplasia Ossificans Progressiva (FOP), also known as a “second skeleton disease” is extremely rare (1: 2000000) and disabling genetic disorder, caused by mutation of ACVR1 gene, a bone morphogenetic protein receptor. Among medical specialties there are no certain, capable to provide not only diagnostics, but also all medical maintenance (assessment and monitoring of extent of damages, the differentiated drug treatment, rehabilitation, contact with adjacent experts). It would be reasonable if the rheumatologist carried out a role of the main attending physician for the patient with FOP. It seems to be a lot of similarities between rheumatic diseases, especially spondyloarthritis (SpA) and FOP in the pathophysiology, clinical manifestation and the therapy approach.Objectives: to present the single-center experience of the FOP patients and to identify similar symptoms in FOP and rheumatic disease.MethodsThe analysis of the large series of patients with FOP, who observed in the rheumatologic clinic.ResultsOur single center experience includes 26 patients with FOP. All 26 patients (13 male and 13 female) had 3 basic FOP clinical manifestations. In 23 patients molecular-genetic tests were performed and typical mutation (Arginine 206) occurred in 22 cases and one had an extremely rare mutation (Glicine 328). 22 (85%) patients had common for FOP massive heterotopic ossifications. 3 of them had formed heterotopic ossification through the X-ray negative stage to visible changes. Among typical phenotypic stigmas were: great toe malformation; thumbs malformation; peripheral osteochondromas; cervical spine abnormalities. Majority of the cases presented some similarities to SpA manifestations: ankylosis of the apophysial joints and vertebral bodies mostly in cervical spine; X-ray/CT evidence of the sacroiliitis in all patients, who were examined (n=8). Because of severe body deformity or metal details after previous surgery intervention there were no possibility to perform MRI in most patients, but we confirm typical sacroiliitis with extended bone edema on MRI in 3 patients. Recurrent episodes of the large joints synoviitis were present in 5 patients. 4 patients demonstrated gradually formation of great toe ankylosis during the follow-up observation. The involution and decreasing of new FOP nodes associated with non-steroidal anti-inflammatory drug intake and/or glucocorticoids therapy were occurred in all patients.Clinical featuresMalefemaleTotal N of patientsSex ratio131326 (1:1)Age of initial manifestations (years) <1819 (35%) 1-96814 (54%) >10033 (11%)Great toe malformation131225 (96%)Thumbs malformation235 (19%)Cervical spine abnormalities12921 (81%)Peripheral osteochondromas8715 (58%)Massive heterotopic ossifications121022 (85%)CT/X-Ray/MRI picture of sacroiliitis2 (of 2)6 (of 6)8 of 8 (100%)ConclusionAppearance of the similarities in FOP and SpA manifestation and the therapy approach could identify FOP as a potential rheumatic disease. Clinical observation of FOP patients could provide the important inf...

Aim to analyze demographic data, clinical features and results of laboratory and instrumental examinations in children with primary and secondary Sjögren syndrome (SS). Materials and methods. The study included all consequently patients, who hospitalized to the pediatric department of V.A. Nasonova Scientific and Research Institute of Rheumatology from January 2013 to December 2018, which verified the diagnosis of the SS. Results. The diagnosis of SS was established in 30 patients, among whom there were only 5 (16.7%) boys, the ratio of boys and girls was 1:5. According to the results of the examination, the following diagnoses were verified: 4 - primary SS, 9 - systemic lupus erythematosus with SS, 10 - juvenile rheumatoid arthritis with SS, 3 - mixed connective tissue disease, 3 - overlap syndrome, 1 - systemic sclerosis with SS. The median age of rheumatic disease onset was 10.4 (7.0; 13.75) years. The median of disease duration at the time of SS verification - 3.0 (0.85; 4.4) years. Recurrent parotitis were observed in 8 patients. 24 pts had isolated involvement of salivary glands, 6 - combined with lacrimal glands. Sicca syndrome was occurred in 8 patients. All patients had systemic manifestations: constitutional abnormalities - 50%, polyarthritis - 83.3%, lymphadenopathy - 73.3%, cutaneous involvement - 60%, pulmonary involvement - 23.3%. Of the hematological disorders, leuko/lymphopenia was more often recorded - in 30%, polyclonal hypergammaglobulinemia - in 26.7% of patients. ANA were detected in all cases, anti-Ro antibodies - 60%, a positive rheumatoid factor - 56.7% of patients. The most common combination of immunological disorders was the presence of ANA, RF and anti-Ro antibodies (40% of patients). The treatment for each patient was justified by the main manifestations and activity of rheumatic disease: 66.7% received nonsteroidal anti - inflammatory drugs, 80% - glucocorticoids, 46.7% - methotrexate, 20% - azathioprine, 43.3% - hydroxychloroquine, 10% - mycophenolatis mofetilum, 3.4% - cyclophosphamide. 66.7% of patients received the treatment of Biologics. Conclusions. Early diagnosis of SS in children with rheumatic diseases significantly affects to the choice of treatment and prognosis. In children the SS has no clinical manifestations for a long time. Such symptoms as a hypergammaglobulinemia, positive RF without persistant arthritis, nonspecific skin lesions, recurrent parotid swelling may help to diagnosis of SS.