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Arthritis Care & Research Mar 2023Observational studies report mixed findings regarding the association between vitamin D and juvenile idiopathic arthritis (JIA) incidence or activity; however, such...
OBJECTIVES
Observational studies report mixed findings regarding the association between vitamin D and juvenile idiopathic arthritis (JIA) incidence or activity; however, such studies are susceptible to considerable bias. Because low vitamin D levels are common within the general population and easily corrected, there is potential public health benefit in identifying a causal association between vitamin D insufficiency and JIA incidence. To limit bias due to confounding and reverse causation, we examined the causal effect of the major circulating form of vitamin D, 25-hydroxy vitamin D (25-[OH]D), on JIA incidence using Mendelian randomization (MR).
METHODS
In this 2-sample MR analysis, we used summary level data from the largest and most recent genome-wide association study of 25-(OH)D levels (sample size 443,734), alongside summary data from 2 JIA genetic studies (sample sizes 15,872 and 12,501), all from European populations. To test and account for potential bias due to pleiotropy, we employed multiple MR methods and sensitivity analyses.
RESULTS
We found no evidence of a causal relationship between genetically predicted 25-(OH)D levels and JIA incidence (odds ratio 1.00 [95% confidence interval (95% CI) 0.76, 1.33] per SD increase in standardized natural-log transformed 25-[OH]D levels). This estimate was consistent across all methods tested. Additionally, there was no evidence that genetically predicted JIA causally influences 25-(OH)D levels (-0.002 SD change in standardized natural-log transformed 25-[OH]D levels per doubling odds in genetically predicted JIA [95% CI -0.006, 0.002]).
CONCLUSION
Given the lack of a causal relationship between 25-(OH)D levels and JIA, population level vitamin D supplementation is unlikely to reduce JIA incidence.
Topics: Humans; Arthritis, Juvenile; Mendelian Randomization Analysis; Genome-Wide Association Study; Vitamin D; Polymorphism, Single Nucleotide
PubMed: 34748291
DOI: 10.1002/acr.24815 -
The Lancet. Child & Adolescent Health Oct 2019The aims of treating juvenile idiopathic arthritis are to elicit treatment response toward remission, while preventing future flares. Understanding patient and disease... (Review)
Review
The aims of treating juvenile idiopathic arthritis are to elicit treatment response toward remission, while preventing future flares. Understanding patient and disease characteristics that predispose young people with this condition to these outcomes would allow the forecasting of disease process and the tailoring of therapies. The strongest predictor of remission is disease category, particularly oligoarthritis, although a few additional clinical predictors of treatment response have been identified. Novel evidence using biomarkers, such as S100 proteins and novel single nucleotide polymorphism data, could add value to clinical models. The future aim of personalised medicine in the treatment of juvenile idiopathic arthritis will be aided with international collaborations, allowing for the analysis of larger datasets with novel biomarker data. Combined clinical and biomarker panels will probably be required for predicting outcomes in such a complex disease.
Topics: Arthritis, Juvenile; Biomarkers; Cohort Studies; Humans; Outcome Assessment, Health Care; Patient-Centered Care; Remission Induction
PubMed: 31331873
DOI: 10.1016/S2352-4642(19)30188-9 -
Clinical and Experimental Rheumatology 2015Juvenile psoriatic arthritis (JPsA) has provided paediatric rheumatologists with a controversial topic for many years. The principal area of contention centres on the... (Review)
Review
Juvenile psoriatic arthritis (JPsA) has provided paediatric rheumatologists with a controversial topic for many years. The principal area of contention centres on the discordance between its treatment as a single diagnostic category in current classification schemes and the demonstration of its heterogeneous nature. A further point of debate is the distinctiveness of JPsA as an entity. Owing to these uncertainties, the concept of JPsA has evolved over the years and there have been several changes in its definition and diagnostic criteria. Recently, strong evidence has been provided that the spectrum of JPsA include at least two distinct subgroups, one that has the same characteristics as early-onset ANA-positive JIA, and another that is part of the spectrum of spondyloarthropathies and resembles the forms of psoriatic arthritis in adults that belong to the same disease family. These findings call for a revision of the classification of childhood arthritis, that refutes the assumptions that children with JPsA constitute a single homogeneous population and that JPsA should be considered an individual disease entity.
Topics: Age of Onset; Arthritis, Juvenile; Arthritis, Psoriatic; Evidence-Based Medicine; Humans; Predictive Value of Tests; Prognosis; Terminology as Topic
PubMed: 26470604
DOI: No ID Found -
Clinical and Experimental Medicine Jul 2023Juvenile idiopathic arthritis (JIA) is a common pediatric rheumatic disease. Renal manifestations have been rarely observed in JIA, although amyloidosis could be a renal... (Review)
Review
Juvenile idiopathic arthritis (JIA) is a common pediatric rheumatic disease. Renal manifestations have been rarely observed in JIA, although amyloidosis could be a renal complication in systemic JIA (sJIA). To investigate renal damage in JIA children and to establish the relationship with treatment. Blood urea nitrogen (BUN), creatinine, cystatin C (CysC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), urinary albumin excretion (UAE), estimated glomerular filtration rate (eGFR), and renal resistive index (RRI) were assessed in 49 JIA children (9 boys/40 girls, mean age 10.3 ± 3.8 years) and in 49 healthy controls (24 boys/25 girls, mean age 11.3 ± 3.4 years). Twenty-two JIA patients were on methotrexate (MTX) therapy (group A) and 27 on biologic drugs (group B). CysC and BUN (respectively, 0.8 ± 0.1 vs. 0.7 ± 0.1 mg/dl; 13.3 ± 2.9 vs. 11.7 ± 1.4 mg/dl) were higher (p ≤ 0.001) whereas creatinine and eGFR (respectively, 0.5 ± 0.1 vs. 0.6 ± 0.1 mg/dl; 99.2 ± 10.5 vs. 122.5 ± 19.8 ml/min/1.73 m) were lower in JIA children as compared to controls (p < 0.001). UAE resulted higher in patients than in controls (p = 0.003). Mean RRI was higher in JIA children than controls (0.7 ± 0.04 vs. 0.6 ± 0.04; p < 0.001). Group B showed higher mean RRI than group A (0.7 ± 0.1 vs. 0.7 ± 0.04; p < 0.001). Associations were found between RRI and ESR, JADAS-27, disease state, BMI-SDS (p < 0.001), CRP (p = 0.003) and eGFR (p = 0.001). JIA children had reduced eGFR, increased UAE and higher RRI values, than controls. RRIs were higher in patients on biologic drugs than MTX group and were associated with inflammation indexes and disease state, suggesting a direct effect of the disease.
Topics: Male; Female; Child; Humans; Adolescent; Arthritis, Juvenile; Creatinine; Methotrexate; Kidney; Inflammation
PubMed: 36129558
DOI: 10.1007/s10238-022-00898-x -
The Orthopedic Clinics of North America Oct 2019Juvenile idiopathic arthritis includes conditions characterized by joint inflammation of unknown etiology lasting longer than 6 weeks in patients younger than... (Review)
Review
Juvenile idiopathic arthritis includes conditions characterized by joint inflammation of unknown etiology lasting longer than 6 weeks in patients younger than 16 years. Diagnosis and medical management are complex and best coordinated by a pediatric rheumatologist. The mainstay of therapy is anti-inflammatory and biologic medications to control pain and joint inflammation. Orthopedic surgical treatment may be indicated for deformity, limb length inequality, or end-stage arthritis. Evaluation of the cervical spine and appropriate medication management in consultation with a patient's rheumatologist are essential in perioperative care. Preoperative planning should take into account patient deformity, contracture, small size, osteopenia, and medical comorbidities.
Topics: Adolescent; Arthritis, Juvenile; Child; Child, Preschool; Combined Modality Therapy; Female; Humans; Orthopedic Surgeons; Patient Care Planning; Patient-Centered Care; Perioperative Care; Rheumatologists
PubMed: 31466663
DOI: 10.1016/j.ocl.2019.06.003 -
Ugeskrift For Laeger Mar 2022During the past 20 years of the biologic era, remission has become a realistic goal when treating children and adolescents with juvenile idiopathic arthritis (JIA).... (Review)
Review
During the past 20 years of the biologic era, remission has become a realistic goal when treating children and adolescents with juvenile idiopathic arthritis (JIA). Studies describing long-term effects and safety are now available for several biologic agents, overall being well tolerated and with acceptable adverse events. No significant association between treatment with biologics and malignancy has been detected. This review finds that although biologics have been a success for most JIA patients, some fail to respond leaving the need for new treatment options and optimal switching between biologics most relevant.
Topics: Adolescent; Antirheumatic Agents; Arthritis, Juvenile; Biological Products; Biological Therapy; Child; Humans; Treatment Outcome
PubMed: 35499221
DOI: No ID Found -
Orthodontics & Craniofacial Research Dec 2023Juvenile idiopathic arthritis (JIA) is the most common inflammatory rheumatic disease of childhood. JIA can affect any joint and the temporomandibular joint (TMJ) is one... (Review)
Review
Juvenile idiopathic arthritis (JIA) is the most common inflammatory rheumatic disease of childhood. JIA can affect any joint and the temporomandibular joint (TMJ) is one of the joints most frequently involved. TMJ arthritis impacts mandibular growth and development and can result in skeletal deformity (convex profile and facial asymmetry), and malocclusion. Furthermore, when TMJs are affected, patients may present with pain at joint and masticatory muscles and dysfunction with crepitus and limited jaw movement. This review aims to describe the role of orthodontists in the management of patients with JIA and TMJ involvement. This article is an overview of evidence for the diagnosis and treatment of patients with JIA and TMJ involvement. Screening for the orofacial manifestation of JIA is important for orthodontists to identify TMJ involvement and related dentofacial deformity. The treatment protocol of JIA with TMJ involvement requires an interdisciplinary collaboration including orthopaedic/orthodontic treatment and surgical interventions for the management of growth disturbances. Orthodontists are also involved in the management of orofacial signs and symptoms; behavioural therapy, physiotherapy and occlusal splints are the suggested treatments. Patients with TMJ arthritis require specific expertise from an interdisciplinary team with members knowledgeable in JIA care. Since disorders of mandibular growth often appear during childhood, the orthodontist could be the first clinician to see the patient and can play a crucial role in the diagnosis and management of JIA patients with TMJ involvement.
Topics: Child; Humans; Adolescent; Orthodontists; Temporomandibular Joint; Temporomandibular Joint Disorders; Arthritis, Juvenile; Mandible
PubMed: 37226648
DOI: 10.1111/ocr.12676 -
Indian Journal of Pediatrics Jan 2016Juvenile idiopathic arthritis (JIA) comprises a group of heterogeneous disorders of chronic arthritis in childhood and remains the commonest pediatric rheumatic disease... (Review)
Review
Juvenile idiopathic arthritis (JIA) comprises a group of heterogeneous disorders of chronic arthritis in childhood and remains the commonest pediatric rheumatic disease associated with significant long-term morbidity. Advances in understanding of the pathogenesis, better definition of disease control/remission measures, and the arrival of biological agents have improved the outcomes remarkably. Methotrexate (Mtx) remains the first-line disease modifying (DMARD) therapy for most children with JIA due to its proven efficacy and safety. Sulphosalazine (SSz) (especially for enthesitis) and leflunomide may also have a secondary role. Tumor necrosis factor inhibitors (TNF-I), alone or in combination with Mtx have shown tremendous benefit in children with polyarticular JIA, enthesitis related arthritis (ERA) and psoriatic arthritis. Tocilizumab appears very efficacious in systemic arthritis and abatacept and tocilizumab also appear to benefit polyarticular JIA; the role of rituximab remains unclear, though clearly beneficial in adult RA. TNF-I with Mtx is also effective in uveitis associated with JIA. Biologicals have demonstrated an impressive safety record in children with JIA, although close monitoring for rare but potentially dangerous adverse events, such as tuberculosis and other infections; paradoxical development of additional autoimmune diseases; and possibly an increased risk of cancers is warranted.
Topics: Antirheumatic Agents; Arthritis, Juvenile; Biological Therapy; Child; Disease Management; Humans; Patient Acuity; Prognosis
PubMed: 26639461
DOI: 10.1007/s12098-015-1966-1 -
The Journal of Pediatrics Oct 2016
Review
Topics: Arthritis, Juvenile; Child; Child, Preschool; Disease Management; Humans
PubMed: 27499217
DOI: 10.1016/j.jpeds.2016.06.056 -
Autoimmunity Reviews Jun 2022Antinuclear antibodies (ANA) detected in juvenile idiopathic arthritis (JIA) sera are considered to be a biomarker for JIA-related uveitis. There is an unclear consensus... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Antinuclear antibodies (ANA) detected in juvenile idiopathic arthritis (JIA) sera are considered to be a biomarker for JIA-related uveitis. There is an unclear consensus on the screening dilutions of ANA as detected by the HEp-2 indirect immunofluorescence assay (IFA) that should be used when predicting the risk of uveitis in JIA. The primary aim of this systematic review and meta-analysis was to summarize the evidence regarding ANA prevalence and performance in JIA and JIA-associated uveitis.
METHODS
A search of five databases identified 1766 abstracts, using the search terms juvenile idiopathic arthritis; pediatric; sensitivity or diagnostic; and ANA. Studies that met inclusion/exclusion criteria were analyzed for the proportion of JIA patients with a positive ANA. Forest plots and pooled estimates were generated for the proportion of JIA patients and those with uveitis who were positive for ANA stratified by screening dilution. Study heterogeneity was also assessed.
RESULTS
Twenty-eight studies met inclusion criteria yielding 6250 unique patients; 5902 had JIA and 348 were healthy controls or were known to have other autoimmune diseases. The most reported IFA serum screening dilution was ≥1:80, representing 41.9% of patients and this screening dilution had the highest proportion of JIA ANA positivity (41.0%; 95% CI 25.0%-57.0%). ANA screening for JIA uveitis had a sensitivity and specificity of ANA at ≥1:40 of 75% (95% CI 46%-100%) and 66% (95% CI 39%-93%), respectively. There was significant study heterogeneity across both JIA subtypes and ANA titres.
CONCLUSIONS
Although there was a large variation of ANA IFA screening dilutions used for investigation of JIA, the most common dilution was 1:80. The current literature has several important deficiencies that are identified in this review requiring additional studies to inform the ANA screening dilutions of clinical value in JIA and JIA-associated uveitis.
Topics: Antibodies, Antinuclear; Arthritis, Juvenile; Child; Fluorescent Antibody Technique, Indirect; Humans; Prevalence; Retrospective Studies; Uveitis
PubMed: 35398272
DOI: 10.1016/j.autrev.2022.103086