Mikhail Kostik

Delineating the Role of Multiple Intraarticular Corticosteroid Injections in the Management of Juvenile Idiopathic Arthritis in the Biologic Era

To investigate the outcome and predicting factors of multiple intraarticular corticosteroid (IAC) injections in children with juvenile idiopathic arthritis (JIA).

Comparing Presenting Clinical Features in 48 Children With Microscopic Polyangiitis to 183 Children Who Have Granulomatosis With Polyangiitis (Wegener's): An ARChiVe Cohort Study

To uniquely classify children with microscopic polyangiitis (MPA), to describe their demographic characteristics, presenting clinical features, and initial treatments in comparison to patients with granulomatosis with polyangiitis (Wegeners) (GPA).

Methotrexate Therapy May Prevent the Onset of Uveitis in Juvenile Idiopathic Arthritis

OBJECTIVE To evaluate whether early treatment with methotrexate (MTX) prevents the onset of uveitis in children with juvenile idiopathic arthritis. STUDY DESIGN The clinical charts of all consecutive patients seen between January 2002 and February 2011 who had a disease duration <1 year at first visit and had received a stable management for at least 2 years with or without MTX were reviewed. Patients who were given systemic medications other than MTX (except nonsteroidal anti-inflammatory drugs) were excluded. Patients with systemic arthritis, rheumatoid factor-positive arthritis, or enthesitis-related arthritis were also excluded. In each patient, the 2-year follow-up period after first visit was examined to establish whether uveitis had occurred. RESULTS A total of 254 patients with a median disease duration of 0.3 year were included. Eighty-six patients (33.9%) were treated with MTX, whereas 168 patients (66.1%) did not receive MTX. During the 2-year follow-up, 211 patients (83.1%) did not develop uveitis, whereas 43 patients (16.9%) had uveitis a median of 1.0 year after the first visit. The frequency of uveitis was lower in MTX-treated than in MTX-untreated patients (10.5% vs 20.2%, respectively, P = .049). Survival analysis confirmed that patients treated with MTX had a lower probability of developing uveitis. CONCLUSION Early MTX therapy may prevent the onset of uveitis in children with juvenile idiopathic arthritis. Because our study may be affected by confounding by indication, the potential of MTX to reduce the incidence of ocular disease should be investigated in a randomized controlled trial.

Comparing presenting clinical features of 48 children with microscopic polyangiitis (MPA) against 183 having granulomatosis with polyangiitis (GPA). An ARChiVe study

To uniquely classify children with microscopic polyangiitis (MPA), to describe their demographic characteristics, presenting clinical features, and initial treatments in comparison to patients with granulomatosis with polyangiitis (Wegeners) (GPA).

Glucocorticoid receptor gene polymorphism and juvenile idiopathic arthritis.

BackgroundThe glucocorticoid receptor gene (NR3C1) has been suggested as a candidate gene affecting juvenile idiopathic arthritis (JIA) course and prognosis. The purpose of this study is to investigate the glucocorticoid receptor gene Bcl I polymorphism (rs41423247) in JIA patients, the genes role in susceptibility to juvenile idiopathic arthritis, and its associations with JIA activity, course and bone mineralization.MethodsOne hundred twenty-two Caucasian children with JIA and 143 healthy ethnically matched controls were studied. We checked markers of clinical and laboratory activity: morning stiffness, Ritchie Articular Index (RAI), swollen joint count (SJC), tender joint count (TJC), physicians visual analog scale (VAS), hemoglobin level (Hb), leukocyte count (L), platelet count (Pl), Westergren erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), albumin, DAS and DAS28. Bone mineralization was measured by dual-energy X-ray absorptiometry (DXA) of lumbar spine L1-L4. Assessments of bone metabolism included osteocalcin, C-terminal telopeptide (CTT), parathyroid hormone (PTH), total and ionized calcium, inorganic phosphate and total alkaline phosphatase (TAP). Bcl I polymorphism was genotyped by polymerase chain reaction restriction fragment length polymorphism.ResultsNo association was observed between glucocorticoid receptor gene polymorphism and the presence or absence of JIA. In girls with JIA, the presence of the G allele was associated with an unfavorable arthritis course, a younger age of onset of arthritis (p = 0.0017), and higher inflammatory activity. The higher inflammatory activity was demonstrated by the following: increased time of morning stiffness (p = 0.02), VAS (p = 0.014), RAI (p = 0.048), DAS (p = 0.035), DAS28 (p = 0.05), Pl (p = 0.003), L (p = 0.046), CRP (p = 0.01). In addition, these patients had bone metabolism disturbances as follows: decreased BA (p = 0.0001), BMC (p = 0.00007), BMD (0.005) and Z score (p = 0.002); and higher levels of osteocalcin (p = 0.03), CTT (p = 0.036), TAP activity (p = 0.01) and ionized calcium (p = 0.017). In boys with JIA, no significant differences were observed related to the polymorphic alleles or genotypes.ConclusionsWe suggest that G allele and the GG genotype of the glucocorticoid receptor gene Bcl I polymorphism contribute to an unfavorable course and low bone mineral density in girls with JIA.

Farber lipogranulomatosis with predominant joint involvement mimicking juvenile idiopathic arthritis

The case of a 10-year-old boy with Farber lipogranulomatosis with predominant joint involvement, subacute, laryngeal and tongue granulomas, microcytic anemia, elevated ESR and CRP, is presented. The boy had no signs of CNS and internal organ involvement. The disease manifested at 6 months; at 11 months the boy had widespread granulomatous polyarthritis with contractures, and juvenile idiopathic arthritis (JIA) was suggested. All antirheumatic therapies failed. Immunologic assessment revealed elevated serum interleukin-1β, increased T-helper, NK and CD25-positive cells, and circulating immune complexes. Our case with predominant rheumatologic manifestations illustrates a differential diagnosis of JIA.

Genetic polymorphisms of collagen type I α1 chain (COL1A1) gene increase the frequency of low bone mineral density in the subgroup of children with juvenile idiopathic arthritis

BackgroundCollagen type I is one of the key proteins involved in the maturation, development and mineralization of bone. Genetic polymorphisms of collagen type I alpha-1 chain (COL1A1) gene are associated with low bone mineral density and higher risk of fractures in adults and children. We hypothesize that the polymorphic alleles and genotypes of COL1A1 gene influence bone mineralization and metabolism in children with juvenile idiopathic arthritis (JIA).MethodsWe recruited 196 children with JIA in our study. Bone mineral density (BMD) was measured by lumbar spine dual-energy X-ray absorptiometry. Osteocalcin, Ca, Ca2+ and inorganic phosphate (Pi) were utilized for the assessment of bone metabolism. Molecular testing: Sp1 (rs1800012) and -1997G/T (rs1107946) polymorphisms of COL1A1 gene were detected RFLP.ResultsNo differences in genotype, allele and haplotype distribution of COL1A1 were detected among children with normal and low BMD (LBMD; <−2 standard deviation). The presence of GG genotype of Sp1 increased the incidence of LBMD in Tanner II to III children (odds ratio (OR) = 9.7 [95% confidence interval (CI), 1.2; 81.7], p = 0.02) as well as GG genotype of -1997G/T increased the frequency of LBMD in Tanner IV to V children (OR = 4.5 [95% CI, 0.9; 22.0], p = 0.048). Tanner I children with -1997GG genotype had lower Ca2+ and osteocalcin and higher Pi compared with carriers of -1997Т allele. Tanner IV to V children with -1997GG genotype had lower BMD and BMD-Z score than carriers of -1997Т.ConclusionsThe evaluation of the biologic effects of the GG Sp1 and GG of -1997G/T polymorphism of COL1A1 has shown negative effect on BMD and mineral turnover related to pubertal stage.

Early Outcomes in Children With Antineutrophil Cytoplasmic Antibody–Associated Vasculitis

To characterize the early disease course in childhood‐onset antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV) and the 12‐month outcomes in children with AAV.

Effect of Biologic Therapy on Clinical and Laboratory Features of Macrophage Activation Syndrome Associated With Systemic Juvenile Idiopathic Arthritis

To assess performance of the 2016 macrophage activation syndrome (MAS) classification criteria for patients with systemic juvenile idiopathic arthritis (JIA) who develop MAS while treated with biologic medications.

A128: Hierarchical Clustering Methodology for Exploration of Proteomic Profile in Tears: Seeking for Markers of Uveitis Associated With Juvenile Idiopathic Arthritis

Uveitis often is the only initial clinical manifestation of JIA for years. There are no reliable markers of JIA‐associated uveitis and impossibility to overcome ocular barriers impede diagnosis and treatment leading to blindness. During the last years the number of proteins identified in tears increased from 200 (Herber et al., 2001) of only 17 (Zhou et al., 2003) different molecular weights (MW) to 491 (de Souza et al., 2006) with 80 chemokines, cytokines, and growth factors (Sack et al., 2005). Objective of the study is to reveal protein markers of JIA‐associated uveitis in tears using high‐resolution mass‐spectrometry and hierarchical clustering methodology.