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Cells Oct 2020Juvenile idiopathic arthritis (JIA) is highly heterogeneous in terms of etiology and clinical presentation with ambiguity in JIA classification. The advance of... (Review)
Review
Juvenile idiopathic arthritis (JIA) is highly heterogeneous in terms of etiology and clinical presentation with ambiguity in JIA classification. The advance of high-throughput omics technologies in recent years has gained us significant knowledge about the molecular mechanisms of JIA. Besides a minor proportion of JIA cases as monogenic, most JIA cases are polygenic disease caused by autoimmune mechanisms. A number of alleles (including both class I and class II genes), and 23 non- genetic loci have been identified of association with different JIA subtypes. Omics technologies, i.e., transcriptome profiling and epigenomic analysis, contributed significant knowledge on the molecular mechanisms of JIA in addition to the genetic approach. New molecular knowledge on different JIA subtypes enables us to reconsider the JIA classification, but also highlights novel therapeutic targets to develop a cure for the devastating JIA.
Topics: Arthritis, Juvenile; Autoimmune Diseases; Epigenome; Genetic Predisposition to Disease; Genome-Wide Association Study; HLA Antigens; Humans; Multifactorial Inheritance; Transcriptome
PubMed: 33076506
DOI: 10.3390/cells9102301 -
Pediatric Rheumatology Online Journal Mar 2021Juvenile Idiopathic Arthritis is one of the most prevalent chronic diseases in children, with an annual incidence of 2-20 cases per 100,000 and a prevalence of 16-150... (Review)
Review
Juvenile Idiopathic Arthritis is one of the most prevalent chronic diseases in children, with an annual incidence of 2-20 cases per 100,000 and a prevalence of 16-150 per 100,000. It is associated with several complications that can cause short-term or long-term disability and reduce the quality of life. Among these, growth and pubertal disorders play an important role. Chronic inflammatory conditions are often associated with growth failure ranging from slight decrease in height velocity to severe forms of short stature. The prevalence of short stature in JIA varies from 10.4% in children with polyarticular disease to 41% of patients with the systemic form, while oligoarthritis is mostly associated with localized excessive bone growth of the affected limb, leading to limb dissymmetry. The pathogenesis of growth disorders is multifactorial and includes the role of chronic inflammation, long-term use of corticosteroids, undernutrition, altered body composition, delay of pubertal onset or slow pubertal progression. These factors can exert a systemic effect on the GH/IGF-1 axis and on the GnRH-gonadotropin-gonadic axis, or a local influence on the growth plate homeostasis and function. Although new therapeutic options are available to control inflammation, there are still 10-20% of patients with severe forms of the disease who show continuous growth impairment, ending in a short final stature. Moreover, delayed puberty is associated with a reduction in the peak bone mass with the possibility of concomitant or future bone fragility. Monitoring of puberty and bone health is essential for a complete health assessment of adolescents with JIA. In these patients, an assessment of the pubertal stage every 6 months from the age of 9 years is recommended. Also, linear growth should be always evaluated considering the patient's bone age. The impact of rhGH therapy in children with JIA is still unclear, but it has been shown that if rhGH is added at high dose in a low-inflammatory condition, post steroids and on biologic therapy, it is able to favor a prepubertal growth acceleration, comparable with the catch-up growth response in GH-deficient patients. Here we provide a comprehensive review of the pathogenesis of puberty and growth disorders in children with JIA, which can help the pediatrician to properly and timely assess the presence of growth and pubertal disorders in JIA patients.
Topics: Adolescent; Arthritis, Juvenile; Child; Growth Disorders; Humans; Puberty
PubMed: 33712046
DOI: 10.1186/s12969-021-00521-5 -
Medicine Mar 2024Juvenile idiopathic arthritis (JIA) is a chronic clinical condition characterized by arthritic features in children under the age of 16, with at least 6 weeks of active... (Review)
Review
Juvenile idiopathic arthritis (JIA) is a chronic clinical condition characterized by arthritic features in children under the age of 16, with at least 6 weeks of active symptoms. The etiology of JIA remains unknown, and it is associated with prolonged synovial inflammation and structural joint damage influenced by environmental and genetic factors. This review aims to enhance the understanding of JIA by comprehensively analyzing relevant literature. The focus lies on current diagnostic and therapeutic approaches and investigations into the pathoaetiologies using diverse research modalities, including in vivo animal models and large-scale genome-wide studies. We aim to elucidate the multifactorial nature of JIA with a strong focus towards genetic predilection, while proposing potential strategies to improve therapeutic outcomes and enhance diagnostic risk stratification in light of recent advancements. This review underscores the need for further research due to the idiopathic nature of JIA, its heterogeneous phenotype, and the challenges associated with biomarkers and diagnostic criteria. Ultimately, this contribution seeks to advance the knowledge and promote effective management strategies in JIA.
Topics: Child; Animals; Humans; Infant; Arthritis, Juvenile; Phenotype; Biomarkers
PubMed: 38552102
DOI: 10.1097/MD.0000000000037567 -
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 -
Medicine Dec 2022Juvenile idiopathic arthritis (JIA) is an inflammatory arthropathy with onset in children younger than 16 years. Treatment is primarily medical; however, surgical... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Juvenile idiopathic arthritis (JIA) is an inflammatory arthropathy with onset in children younger than 16 years. Treatment is primarily medical; however, surgical interventions, such as arthroscopic or open synovectomy, can be beneficial. Many studies have investigated synovectomy in JIA, but the results of these studies have not been synthesized to our knowledge. Therefore, we performed a systematic review of the literature reporting synovectomy as a treatment for JIA to provide clinical recommendations regarding its risks and benefits.
METHODS
On March 8, 2022, we searched the Cochrane Library, Embase, PubMed, Scopus, and Web of Science for studies evaluating clinical outcomes of open or arthroscopic synovectomy to treat JIA in patients younger than 18 years. We included only studies published in English and excluded studies of synovectomy to treat other arthropathies, septic arthritis, hemophilia, or foreign body arthropathy. The level of evidence for included studies was determined by using the Oxford Centre for Evidence-Based Medicine criteria. We qualitatively analyzed clinical outcomes data, including patient-reported pain relief, rates of symptom recurrence, and postoperative complications.
RESULTS
Of 428 articles assessed, 14 were included in our analysis. One was a randomized trial, 1 was a case-control study, and all others were case-series. Studies consistently reported that synovectomy was associated with improved function and decreased pain postoperatively. However, comparisons with modern medical therapy were lacking. Rates of arthritis recurrence varied, with increasing symptom recurrence with longer follow-up and re-synovectomy rates up to 15%. Oligoarticular disease and early disease course were associated with better response to synovectomy, whereas systemic and polyarticular disease were associated with poor response. Stiffness requiring manipulation under anesthesia was the most common complication (4% of all included patients).
CONCLUSION
Although synovectomy is associated with positive functional outcomes and pain reduction postoperatively, there was inadequate comparison thus inadequate evidence to recommend it over modern medical therapy. The current literature suggests that synovectomy should be offered only to patients for whom medical management has failed, while noting the risks of decreased range of motion and symptom recurrence over time.
Topics: Child; Humans; Arthritis, Juvenile; Synovectomy; Case-Control Studies; Knee Joint; Joint Diseases; Pain; Randomized Controlled Trials as Topic
PubMed: 36626489
DOI: 10.1097/MD.0000000000032278 -
The Journal of Clinical Pediatric... Sep 2023Although periodontal diseases have been widely reported in patients with juvenile idiopathic arthritis (JIA), their association with JIA remains controversial. This... (Meta-Analysis)
Meta-Analysis
Although periodontal diseases have been widely reported in patients with juvenile idiopathic arthritis (JIA), their association with JIA remains controversial. This systematic review and meta-analysis aimed to evaluate the association between JIA and periodontal diseases to facilitate oral health management and periodontal disease prevention in JIA patients. We conducted a comprehensive search of Web of Science, Cochrane Library, PubMed, Embase, Chinese Scientific and Technological Journal (VIP) database, Wan Fang Data, China National Knowledge Infrastructure (CNKI), and China Biomedical Literature Database (CBM) up to 30 September 2022, without publication dates or language restrictions. Two authors independently evaluated observational studies for inclusion, and the quality of the included studies was assessed using the Newcastle Ottawa Scale (NOS) and the Agency for Healthcare Research and Quality (AHRQ). Continuous variables are presented as mean difference (MD) and 95% confidence interval (CI). Parameters of the simplified oral hygiene index (OHI-S), plaque index (PI), gingival index (GI), clinical attachment loss (CAL), and probing depth (PD) were considered as outcome measures and were compared between JIA patients and healthy controls. The initial search comprised 15 studies with a total of 1537 individuals. The meta-analysis showed the parameters of OHI-S (MD = 0.12, 95% CI: 0.04-0.19, = 0.002), PI (MD = 2.08, 95% CI: 1.67-2.50, < 0.00001), GI (MD = 0.50, 95% CI: 0.17-0.82, = 0.003), CAL (MD = 0.22, 95% CI: 0.01-0.43, = 0.04), and PD (MD = 1.42, 95% CI: 0.08-2.77, = 0.04) in JIA patients were significantly higher than those of healthy controls. All of the included studies were of high quality. This systematic review and meta-analysis showed a possible association between JIA and periodontal diseases. Therefore, it is recommended to continuously pay attention to the periodontal health of JIA patients and fully explore the underlying mechanism.
Topics: United States; Humans; Arthritis, Juvenile; Periodontal Diseases; Administration, Oral; Databases, Factual; Oral Health
PubMed: 37732432
DOI: 10.22514/jocpd.2023.050 -
Nutrients Apr 2022Vitamin D has been implicated in the pathogenesis of skeletal disorders and various autoimmune disorders. Vitamin D can be consumed from the diet or synthesized in the... (Review)
Review
Vitamin D has been implicated in the pathogenesis of skeletal disorders and various autoimmune disorders. Vitamin D can be consumed from the diet or synthesized in the skin upon ultraviolet exposure and hydroxylation in the liver and kidneys. In its bioactive form, vitamin D exerts a potent immunomodulatory effect and is important for bone health. Juvenile idiopathic arthritis (JIA) is a collection of inflammatory joint diseases in children that share the manifestation of inflamed synovium, which can result in growth arrest, articular deformity, bone density loss, and disability. To evaluate the potential effect of vitamin D on JIA disease manifestations and outcomes, we review the role of vitamin D in bone metabolism, discuss the mechanism of vitamin D in modulating the innate and adaptive immune systems, evaluate the clinical significance of vitamin D in patients with JIA, and summarize the supplementation studies.
Topics: Arthritis, Juvenile; Bone Density; Bone Diseases, Metabolic; Child; Dietary Supplements; Humans; Vitamin D; Vitamin D Deficiency; Vitamins
PubMed: 35458099
DOI: 10.3390/nu14081538 -
Nature Reviews. Rheumatology May 2021Chronic inflammatory arthritis in childhood is heterogeneous in presentation and course. Most forms exhibit clinical and genetic similarity to arthritis of adult onset,... (Review)
Review
Chronic inflammatory arthritis in childhood is heterogeneous in presentation and course. Most forms exhibit clinical and genetic similarity to arthritis of adult onset, although at least one phenotype might be restricted to children. Nevertheless, paediatric and adult rheumatologists have historically addressed disease classification separately, yielding a juvenile idiopathic arthritis (JIA) nomenclature that exhibits no terminological overlap with adult-onset arthritis. Accumulating clinical, genetic and mechanistic data reveal the critical limitations of this strategy, necessitating a new approach to defining biological categories within JIA. In this Review, we provide an overview of the current evidence for biological subgroups of arthritis in children, delineate forms that seem contiguous with adult-onset arthritis, and consider integrative genetic and bioinformatic strategies to identify discrete entities within inflammatory arthritis across all ages.
Topics: Arthritis, Juvenile; Child; Computational Biology; Humans; Phenotype; Polymorphism, Single Nucleotide; Terminology as Topic
PubMed: 33731872
DOI: 10.1038/s41584-021-00590-6 -
Medicina (Kaunas, Lithuania) Oct 2022: Interleukin-17 (IL-17) is a cytokine family consisting of six members and five specific receptors. IL-17A was the first member to be identified in 1993. Since then,... (Review)
Review
: Interleukin-17 (IL-17) is a cytokine family consisting of six members and five specific receptors. IL-17A was the first member to be identified in 1993. Since then, several studies have elucidated that IL-17 has predominantly pro-inflammatory activity and that its production is involved in both the defense against pathogens and the genesis of autoimmune processes. : In this review, we provide an overview of the role of interleukin-17 in the pathogenesis of juvenile idiopathic arthritis (JIA) and its relationship with IL-23, the so-called IL-23-IL-17 axis, by reporting updated findings from the scientific literature. Strong evidence supports the role of interleukin-17A in the pathogenesis of JIA after the deregulated production of this interleukin by both T helper 17 (Th17) cells and cells of innate immunity. The blocking of IL-17A was found to improve the course of JIA, leading to the approval of the use of the human anti-IL17A monoclonal antibody secukinumab in the treatment of the JIA subtypes juvenile psoriatic arthritis (JPsA) and enthesitis-related arthritis (ERA). IL-17A plays a central role in the pathogenesis of JIA. Blocking its production with specific biologic drugs enables the effective treatment of this disabling childhood rheumatic disease.
Topics: Humans; Child; Arthritis, Juvenile; Interleukin-17; Cytokines; Immunity, Innate; Interleukin-23
PubMed: 36363508
DOI: 10.3390/medicina58111552 -
Rheumatology (Oxford, England) Nov 2019Systemic juvenile idiopathic arthritis and adult-onset Still's disease are rare autoinflammatory disorders with common features, supporting the recognition of these... (Review)
Review
Systemic juvenile idiopathic arthritis and adult-onset Still's disease are rare autoinflammatory disorders with common features, supporting the recognition of these being one disease-Still's disease-with different ages of onset. Anakinra was recently approved by the European Medicines Agency for Still's disease. In this review we discuss the reasoning for considering Still's disease as one disease and present anakinra efficacy and safety based on the available literature. The analysis of 27 studies showed that response to anakinra in Still's disease was remarkable, with clinically inactive disease or the equivalent reported for 23-100% of patients. Glucocorticoid reduction and/or stoppage was reported universally across the studies. In studies on paediatric patients where anakinra was used early or as first-line treatment, clinically inactive disease and successful anakinra tapering/stopping occurred in >50% of patients. Overall, current data support targeted therapy with anakinra in Still's disease since it improves clinical outcome, especially if initiated early in the disease course.
Topics: Adult; Antirheumatic Agents; Arthritis, Juvenile; Child; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Approval; Female; Humans; Interleukin 1 Receptor Antagonist Protein; Male; Patient Safety; Severity of Illness Index; Still's Disease, Adult-Onset; Treatment Outcome
PubMed: 31769856
DOI: 10.1093/rheumatology/kez350