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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 -
Seminars in Musculoskeletal Radiology Apr 2018We discuss the imaging of several juvenile inflammatory arthropathies including juvenile idiopathic arthritis, juvenile systemic lupus erythematosus, juvenile... (Review)
Review
We discuss the imaging of several juvenile inflammatory arthropathies including juvenile idiopathic arthritis, juvenile systemic lupus erythematosus, juvenile scleroderma, juvenile dermatomyositis, and chronic recurrent multifocal osteomyelitis. Juvenile idiopathic arthritis is the most common autoimmune chronic systemic disease of connective tissue in children. The remaining systemic juvenile connective tissue diseases are rare. However, they require early diagnosis and initiation of treatment to prevent injury, not only to the musculoskeletal system but also to the internal organs, and even death. Imaging of juvenile inflammatory arthropathies has relied for years on radiography. Recent advances in disease-modifying drugs have led to a greater emphasis on the detection of early inflammation not evident on plain radiography. Ultrasound examination allows for the early recognition of the disease process in the soft tissues. Magnetic resonance imaging detects early inflammatory changes involving the soft tissues, the subcortical bone of peripheral joints, the spine, and entheses.
Topics: Adolescent; Arthritis, Juvenile; Child; Dermatomyositis; Humans; Lupus Erythematosus, Systemic; Scleroderma, Systemic
PubMed: 29672804
DOI: 10.1055/s-0038-1639468 -
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 British Journal of Radiology May 2017Juvenile idiopathic arthritis (JIA) is a heterogeneous condition and an important cause of acquired disability in children. Evidence supports early treatment to prevent... (Review)
Review
Juvenile idiopathic arthritis (JIA) is a heterogeneous condition and an important cause of acquired disability in children. Evidence supports early treatment to prevent future complications. This relies on prompt diagnosis, achieved by a high index of clinical suspicion and supportive evidence, including the detection of joint and or tendon inflammation. Ultrasound is a readily accessible, well-tolerated, safe and accurate modality for assessing joints and the surrounding soft tissues. It can also be used to guide therapy into those joints and tendon sheaths resistant to systemic treatments. Ultrasound imaging is highly operator dependent, and the developing skeleton poses unique challenges in interpretation with sonographic findings that can mimic pathology and vice versa. Ultrasound technology has been rapidly improving and is more accessible than ever before. In this article, we review the normal appearances, highlight potential pitfalls and present the key pathological findings commonly seen in JIA.
Topics: Adolescent; Arthritis, Juvenile; Child; Humans; Ultrasonography
PubMed: 28291375
DOI: 10.1259/bjr.20160920 -
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 -
Rheumatology International Jul 2023Systemic juvenile idiopathic arthritis (S-JIA) is a rare but potentially life threatening autoinflammatory condition of childhood. Given the limited data on S-JIA from...
Systemic juvenile idiopathic arthritis (S-JIA) is a rare but potentially life threatening autoinflammatory condition of childhood. Given the limited data on S-JIA from the Australasian region, we investigated the epidemiological characteristics and long-term disease outcome in S-JIA. All hospitalised patients under the age of 16 years registered with ICD-10-AM code M08.2 in in the period 1999-2014 were identified in longitudinally linked administrative health data across all Western Australian (WA) hospitals. Incidence and point prevalence estimate were per 100,000 population with Poisson regression to analyse the incidence trend. Readmissions with S-JIA as primary diagnosis were considered flares with rates for flare and other complication reported per 100 person years with 95% confidence intervals (CI). Annual S-JIA incidence was 0.61/100,000 (CI 0.28-1.25) (46 incident cases, 71.7% girls, median age 6.5 years) and stable over time as S-JIA point prevalence reached 7.15/100,000 (CI 5.29-7.45) at the end of study. Most incident cases were diagnosed in winter and spring, but documented preceding infections were rare. During a median follow-up of 8 years, disease flares occurred in 24% of patients with higher flares rate in boys (58.3; CI 44.5-74.9) than girls (14.7; CI 9.9-20.9). No deaths occurred and arthroplasty was the main, but uncommon S-JIA complication (4%). However, readmission (86.3; CI 76.4-97.2) and ED visit (73.3; CI 64.2-83.4) rates for illnesses other than S-JIA were substantial. S-JIA is as rare in WA as in other regions and while s-JIA incurred no deaths in the era of biologics, it associated with a significant long-term burden of (co-) morbidity.
Topics: Male; Female; Humans; Child; Adolescent; Arthritis, Juvenile; Western Australia; Australia; Comorbidity; Biological Products
PubMed: 36988674
DOI: 10.1007/s00296-023-05318-1 -
Journal of Autoimmunity Nov 2015Juvenile idiopathic arthritis (JIA) is the most common chronic inflammatory arthropathy of childhood. Juvenile idiopathic arthritis is believed to be a complex genetic... (Review)
Review
Juvenile idiopathic arthritis (JIA) is the most common chronic inflammatory arthropathy of childhood. Juvenile idiopathic arthritis is believed to be a complex genetic trait influenced by both genetic and environmental factors. Twin and family studies suggest a substantial role for genetic factors in the predisposition to JIA. Describing the genetics is complicated by the heterogeneity of JIA; the International League of Associations for Rheumatology (ILAR) has defined seven categories of JIA based on distinct clinical and laboratory features. Utilizing a variety of techniques including candidate gene studies, the use of genotyping arrays such as Immunochip, and genome wide association studies (GWAS), both human leukocyte antigen (HLA) and non-HLA susceptibility loci associated with JIA have been described. Several of these polymorphisms (e.g. HLA class II, PTPN22, STAT4) are shared with other common autoimmune conditions; other novel polymorphisms that have been identified may be unique to JIA. Associations with oligoarticular and RF-negative polyarticular JIA are the best characterized. A strong association between HLA DRB1:11:03/04 and DRB1:08:01, and a protective effect of DRB1:15:01 have been described. HLA DPB1:02:01 has also been associated with oligoarticular and RF-negative polyarticular JIA. Besides PTPN22, STAT4 and PTPN2 variants, IL2, IL2RA, IL2RB, as well as IL6 and IL6R loci also harbor variants associated with oligoarticular and RF-negative polyarticular JIA. RF-positive polyarticular JIA is associated with many of the shared epitope encoding HLA DRB1 alleles, as well as PTPN22, STAT4 and TNFAIP3 variants. ERA is associated with HLA B27. Most other associations between JIA categories and HLA or non-HLA variants need confirmation. The formation of International Consortia to ascertain and analyze large cohorts of JIA categories, validation of reported findings in independent cohorts, and functional studies will enhance our understanding of the genetic underpinnings of JIA.
Topics: Alleles; Animals; Arthritis, Juvenile; Genetic Loci; Genetic Predisposition to Disease; Genome-Wide Association Study; HLA Antigens; Humans; Immunogenetics; Phenotype
PubMed: 26305060
DOI: 10.1016/j.jaut.2015.08.002