Prevalence of the main rheumatic diseases in the Republic of Sakha (Yakutia) [RS(Y)], one of the regions of the Russian Federation, differs from the other regions of the Russian Federation due to its ethnic and geographic features. Knowledge regarding the prevalence and structure of juvenile idiopathic arthritis (JIA) allows us to shape the work of the pediatric rheumatology service in the region correctly, and optimize the healthcare system and the need for medications.

To describe the epidemiological, demographic, clinical, and laboratory characteristics of children with JIA in the RS(Y) and evaluate the main outcomes.

This retrospective cohort study assessed all the data from the medical histories of the patients (n = 225) diagnosed with JIA (2016-2023) in the Cardiorheumatology Department of the M.E. Nikolaev National Center of Medicine. Pearson's χ² test, Fisher's exact test, Mann–Whitney and Kruskal-Wallis tests were used for statistical analyses.

The ethnic prevalence of JIA is higher in Sakha than in Russian children at 110.1 per 100000 children and 69.4 per 100000 children, respectively. The prevalence of JIA among boys and girls in Sakha was similar, unlike in Russians, where the number of girls predominated. The JIA categories were as follows: (1) Systemic arthritis: 3.5%; (2) Oligoarthritis (persistent and extended): 33.8%; (3) Rheumatoid factor (RF) (+) polyarthritis: 0.9%; (4) RF (-) polyarthritis: 14.7%; (5) Enthesitis-related arthritis (ERA): 44%; and (6) Psoriatic arthritis: 3.1%. Prevalence of the ERA category was 4.4 times higher in Sakha children, but the prevalence of systemic arthritis was 2.9 times lower compared to Russians (P = 0.0005). The frequency of uveitis was 10.2%, and the frequency of human leukocyte antigen (HLA) B27 was 39.6% in JIA children. Biologic treatment was received by 40.4% of JIA children and 45.3% achieved remission.

Higher JIA prevalence, male and ERA predominance, related to a higher frequency of HLA B27 are typical in RS(Y). These data might improve the pediatric rheumatology health service.

• Juvenile idiopathic arthritis
• Human leukocyte antigen B27
• Seronegative spondyloarthritis
• Enthesitis-related arthritis
• Epidemiology
• Arthritis
• Yakutia
• Sakha
• Human leukocyte antigen B27-associated arthritis
• Ethnic variation

• BMI
• Biologics
• Height
• Juvenile idiopathic arthritis
• Weight
• growth

• Articular Damage
• India
• JADI-A
• JADI-E
• JIA
• Resource-limited Settings

• Articular damage
• Children
• Damage
• Disability
• Juvenile idiopathic arthritis

• ankylosing spondylitis
• enthesitis-related arthritis
• medical biology
• rheumatology
• spondyloarthritides

• Global health
• Health disparities
• Lower to middle-income countries
• Pediatric rheumatology

Classical alleles of the human leukocyte antigen (HLA) complex have been linked to specific entities of pediatric noninfectious uveitis, yet genetic predisposition encoded by the HLA super-locus across the patient population remains understudied.

We performed next-generation full-length sequencing of HLA-A, HLA-B, HLA-C, HLA-DPB1, HLA-DQB1, and HLA-DRB1 in 280 cases. Dense genotype data from 499 Dutch controls from Genome of the Netherlands were imputed using an HLA-specific reference panel (n = 5225 samples from European ancestry). Cases and controls were compared using logistic regression models adjusting for sex.

In total, 179 common and rare alleles were detected. Considering all cases and controls, HLA-DQB1*04:02 and HLA-DRB1*08:01 were identified as the principal HLA association, which was mainly driven by 92 cases with juvenile idiopathic arthritis-associated uveitis (JIA-U). The HLA-DQB1*04:02-HLA-DRB1*08:01 haplotype was also the primary association for the phenotypically similar idiopathic chronic anterior uveitis without arthritis (CAU). Also, HLA-DQB1*05:03 was an independent risk allele for CAU, but not in JIA-U. Analysis of 185 cases with other forms of uveitis revealed HLA-wide associations (P < 2.79 × 10⁻⁴) for HLA-DRB1*01:02, HLA-DRB1*04:03, and HLA-DQB1*05:03, which could be primarily attributed to cases with panuveitis. Finally, amino acid substitution modeling revealed that aspartic acid at position 57 that distinguishes the risk allele HLA-DQB1*05:03 (for CAU and panuveitis) from nonrisk alleles, significantly increased the binding capacity of naturally presented ligands to HLA-DQ.

These results uncovered novel shared HLA associations among clinically distinct phenotypes of pediatric uveitis and highlight genetic predisposition affecting the antigen presentation pathway.

Juvenile spondyloarthritis (JSpA) refers to a diverse spectrum of immune-mediated inflammatory arthritides whose onset occurs in late childhood and adolescence. Like its adult counterpart, JSpA is typified by a strong association with human leukocyte antigen-B27 (HLA-B27) and potential axial involvement, while lacking rheumatoid factor (RF) and distinguishing autoantibodies. A characteristic manifestation of JSpA is enthesitis (inflammation of insertion sites of tendons, ligaments, joint capsules or fascia to bone), which is commonly accompanied by bone resorption and new bone formation at affected sites. In this Review, advances in the role of HLA-B27, enthesitis and its associated osteoproliferation in JSpA pathophysiology and treatment options will be discussed. A deeper appreciation of how these elements contribute to the JSpA disease mechanism will better inform diagnosis, prognosis and therapy, which in turn translates to an improved quality of life for patients.

• HLA-B27
• enthesitis
• enthesitis related arthritis
• juvenile arthritis
• osteogenesis
• spondyloarthritis

Introduction: Enthesitis-related Arthritis (ERA) is a specific category of juvenile idiopathic arthritis (JIA) characterized by axial and/or peripheral arthritis, and enthesitis, although other different extra-articular manifestations may encompass its clinical spectrum.

Materials and Methods: In order to examine if ERA-JIA with extra-articular involvement may represent a different entity from ERA without extra-articular involvement, we performed a retrospective, observational, monocentric study, in a cohort of ERA patients followed between 2001 and September 2020 at the Pediatric Rheumatology Unit of Meyer Children Hospital of Florence. We analyzed the demographic, clinical, laboratory and imaging data at the disease onset, as well as after 3, 6, and 12 months follow up.

Results: We have enrolled 53 patients, 33 males. At the time of diagnosis, average age was 10.9 years, 53 patients had active arthritis and 25 active enthesitis. The middle foot involvement was present in 20 patients. Twenty-five children achieved clinical remission on medication. Extra-articular manifestations were observed in 14 patients, of whom 3 had inflammatory bowel disease, 5 uveitis, one uveitis associated with Crohn disease, 4 SAPHO syndrome, one celiac disease. The cohort was stratified according to the presence/absence of extra-articular manifestations. It was observed that middle foot involvement was more frequent in patients with no extra-articular manifestations (18/39 vs. 2/14; χ² = 4.45, p = 0.05). Additionally, patients presenting extra-articular manifestation needed more frequently (12/14 vs. 21/39, χ²= 4.45, p = 0.05), and preciously (months: 3.7 ± 5.4 vs. 16.7 ± 26.5, p = 0.02), treatment with biologic agents. Finally, these patients achieved belatedly (months: 31.6 ± 32.3 vs. 22.9 ± 18.3, p = 0.01) and less frequently (3/14 vs. 22/39; χ²= 5.50, p = 0.03) the clinical remission on medication. Eventually, extra-articular involvement inversely correlated with the middle-foot arthritis (ρ_s −0.29, p = 0.03), the chance to achieve remission on medication (ρ_s −0.31 e p = 0.02), as well as the chance to keep overall remission, with and without medication (ρ_s −0.28, p = 0.04).

Conclusion: In our cohort, children diagnosed with ERA-JIA at the onset of disease and then developed extra-articular manifestations show the absence of middle foot involvement and worse prognosis with an early need for the use of biologic agents, and overall low chance to achieve remission.

• JIA
• biologic
• children
• enthesitis-related arthritis
• extra-articular
• midfoot
• sacroiliitis

Objective. To describe the clinical characteristics, predictors and treatment of children with Enthesitis Related Arthritis (ERA) in a Singapore longitudinal cohort over 11 years. Methods. ERA patients were recruited from our registry (2009–2019). Nonparametric descriptive statistics including median (interquartile range, IQR) were used to describe data. Kaplan–Meier survival and logistic/Cox regression analyses were used to estimate the probabilities and determine predictors of clinical variables, respectively. The significance level was set at <0.05. Results. One hundred and forty-six ERA patients (87% male, 82% Chinese) were included. Median onset age was 11.9 years (IQR 9.4–14.0) and median disease duration was 4.9 years (IQR 2.6–8.3). Family history of Human Leukocyte Antigen (HLA)-B27 associated diseases was positive in 7.5%. Acute uveitis occurred in 3.4%. Oligoarthritis was present in 89.7%. Hip, knee and ankle joints were among the most common joints involved. One-fourth had enthesitis at diagnosis (Achilles tendon entheses, 82.9%). Sacroiliitis occurred in 61%. Probabilities of sacroiliitis development were 0.364, 0.448 and 0.578 at 1, 2 and 5 years after onset, respectively. Negative HLA-B27, female, older age at onset and hip arthritis at diagnosis were associated with shorter time for sacroiliitis development (p = 0.001–0.049). Methotrexate (MTX) remained the most common disease modifying anti-rheumatic drug (DMARD) used (77.4%). However, 77.9% required anti-TNF (aTNF) therapy secondary to MTX failure. Among MTX-treated sacroiliitis patients, 85.3% failed, requiring aTNF, as compared to 63.2%patients without axial disease. Longer duration to diagnosis (p = 0.038) and MTX use (p = 0.007) predicted aTNF therapy. None had joint deformity. Conclusions. This study underscores differences in ERA clinical characteristics, predictors and treatment responses. Our ERA population had many unique findings but good functional outcomes.

• Singapore
• Southeast Asia
• enthesitis-related arthritis
• juvenile idiopathic arthritis
• predictors
• treatment

• Juvenile idiopathic arthritis
• Outcomes
• Predictors
• Singapore
• Southeast Asia
• Treatment

• Antirheumatic Agents/therapeutic use
• Arthritis, Juvenile/drug therapy
• Arthritis, Juvenile/epidemiology
• Child
• Female
• Humans
• Longitudinal Studies
• Male
• Singapore/epidemiology
• Treatment Outcome
• Young Adult