Juvenile idiopathic arthritis: from aetiopathogenesis to therapeutic approaches.
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ABSTRACT:
SUBMITTER: Zaripova LN
PROVIDER: S-EPMC8383464 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Pediatric patients with early onset (before the age of 6 years), antinuclear antibody positive, oligoarticular or polyarticular juvenile idiopathic arthritis (JIA), and some children with no arthritis may develop chronic, anterior uveitis. Recent recommendations insist on the need to perform slit lamp examination every 3 months for at least 5 years in early onset JIA patients in order to diagnose uveitis before complications develop. Local steroid therapy is usually the first-line treatment. However, in patients requiring steroid eye drops for several months, systemic immunomodulatory therapy is indicated. Methotrexate (MTX) is then prescribed in most cases; however, some patients also need anti-tumor necrosis factor alpha monoclonal antibody therapy and, in some cases, other biologics to control uveitis and avoid long-term ocular damage. Expert ophthalmologists and pediatricians must be involved in taking care of such patients. Immunomodulatory treatment must not be too easily interrupted and may even be intensified in some cases, particularly if there is a need for optimal disease control before ophthalmologic surgery. In good responders to MTX and/or biologics, treatment must be maintained at least 1 year, possibly even 2 years after achieving remission before tapering treatment intensity.
| S-EPMC8269439 | biostudies-literature
Project description:Juvenile idiopathic arthritis (JIA) is a group of disorders characterized by arthritis persisting for at least 6 weeks with onset before the age of 16 years. Within this cluster of conditions, the polyarticular form (involving more than four joints within the first 6 months) is further divided based on the presence of rheumatoid factor. Children with polyarticular JIA pose unique diagnostic and therapeutic challenges compared to children with involvement of fewer joints. Polyarticular JIA patients tend to have a more refractory course and therefore are at increased risk for joint damage, resulting in poorer functional outcomes and decreased quality of life. Although the ability to treat this disorder continues to improve, especially with the advent of biologic agents, there is still much about the epidemiology and pathogenesis of polyarticular JIA that is unknown. The epidemiology of polyarticular JIA varies worldwide with a vast difference in reported cases between different global regions as well as within individual countries. Several genetic risk loci have been identified conferring increased susceptibility to JIA, many within the human leukocyte antigen region. Beyond the genome, environmental factors also seem to contribute to the etiology of polyarticular JIA. This review article will focus on the epidemiology and current treatments of polyarticular JIA and briefly discuss genetic and environmental influences on the pathogenesis of JIA as well as new and emerging therapies.
| S-EPMC4216020 | biostudies-other
Project description:OBJECTIVES:Juvenile idiopathic arthritis (JIA) is a heterogeneous group of conditions unified by the presence of chronic childhood arthritis without an identifiable cause. Systemic JIA (sJIA) is a rare form of JIA characterised by systemic inflammation. sJIA is distinguished from other forms of JIA by unique clinical features and treatment responses that are similar to autoinflammatory diseases. However, approximately half of children with sJIA develop destructive, long-standing arthritis that appears similar to other forms of JIA. Using genomic approaches, we sought to gain novel insights into the pathophysiology of sJIA and its relationship with other forms of JIA. METHODS:We performed a genome-wide association study of 770 children with sJIA collected in nine countries by the International Childhood Arthritis Genetics Consortium. Single nucleotide polymorphisms were tested for association with sJIA. Weighted genetic risk scores were used to compare the genetic architecture of sJIA with other JIA subtypes. RESULTS:The major histocompatibility complex locus and a locus on chromosome 1 each showed association with sJIA exceeding the threshold for genome-wide significance, while 23 other novel loci were suggestive of association with sJIA. Using a combination of genetic and statistical approaches, we found no evidence of shared genetic architecture between sJIA and other common JIA subtypes. CONCLUSIONS:The lack of shared genetic risk factors between sJIA and other JIA subtypes supports the hypothesis that sJIA is a unique disease process and argues for a different classification framework. Research to improve sJIA therapy should target its unique genetics and specific pathophysiological pathways.
| S-EPMC5530341 | biostudies-literature
Project description:In juvenile idiopathic arthritis (JIA), there are now more than 25 regions represented by single nucleotide polymorphisms that show strong genetic associations. The causal variants and corresponding functions have not yet been defined for the majority of these regions. Here, we review current JIA association findings and the recent progress in the annotation of noncoding portion of the human genome as well as the new technologies necessary to apply this knowledge to JIA association findings.An international collaboration was able to amass sufficient numbers of JIA and control samples to identify significantly robust genetic associations for JIA. The Encyclopedia of DNA Elements project and the National Institutes of Health (NIH) Roadmap Epigenetics Program have now annotated more than 80% of the noncoding genome, important in understanding the impact of risk loci, the majority of which fall outside of protein coding regions. Recent technological advances in high throughput sequencing, chromatin structure determination, transcription factor and enhancer binding site mapping and genome editing will likely provide a basis for understanding JIA genetic risk.Understanding the role of genetic variation in the cause of JIA will provide insight for disease mechanism and may explain disease heterogeneity between JIA subtypes and between autoimmune diseases in general.
| S-EPMC4445412 | biostudies-literature
Project description:Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease of childhood, with JIA-associated uveitis its most common extra-articular manifestation. JIA-associated uveitis is a potentially sight-threatening condition and thus carries a considerable risk of morbidity. The aetiology of the condition is autoimmune in nature with the predominant involvement of CD4(+) T cells. However, the underlying pathogenic mechanisms remain unclear, particularly regarding interplay between genetic and environmental factors. JIA-associated uveitis comes in several forms, but the most common presentation is of the chronic anterior uveitis type. This condition is usually asymptomatic and thus screening for JIA-associated uveitis in at-risk patients is paramount. Early detection and treatment aims to stop inflammation and prevent the development of complications leading to visual loss, which can occur due to both active disease and burden of disease treatment. Visually disabling complications of JIA-associated uveitis include cataracts, glaucoma, band keratopathy and macular oedema. There is a growing body of evidence for the early introduction of systemic immunosuppressive therapies in order to reduce topical and systemic glucocorticoid use. This includes more traditional treatments, such as methotrexate, as well as newer biological therapies. This review highlights the epidemiology of JIA-associated uveitis, the underlying pathogenesis and how affected patients may present. The current guidelines and criteria for screening, diagnosis and monitoring are discussed along with approaches to management.
| S-EPMC4848803 | biostudies-other
Project description:ObjectiveTo develop treatment recommendations for children with juvenile idiopathic arthritis manifesting as non-systemic polyarthritis, sacroiliitis, or enthesitis.MethodsThe Patient/Population, Intervention, Comparison, and Outcomes (PICO) questions were developed and refined by members of the guideline development teams. A systematic review was conducted to compile evidence for the benefits and harms associated with treatments for these conditions. GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology was used to rate the quality of evidence. A group consensus process was conducted among the Voting Panel to generate the final recommendations and grade their strength. A Parent and Patient Panel used a similar consensus approach to provide patient/caregiver preferences for key questions.ResultsThirty-nine recommendations were developed (8 strong and 31 conditional). The quality of supporting evidence was very low or low for 90% of the recommendations. Recommendations are provided for the use of nonsteroidal antiinflammatory drugs, disease-modifying antirheumatic drugs, biologics, and intraarticular and oral glucocorticoids. Recommendations for the use of physical and occupational therapy are also provided. Specific recommendations for polyarthritis address general medication use, initial and subsequent treatment, and adjunctive therapies. Good disease control, with therapeutic escalation to achieve low disease activity, was recommended. The sacroiliitis and enthesitis recommendations primarily address initial therapy and adjunctive therapies.ConclusionThis guideline provides direction for clinicians, caregivers, and patients making treatment decisions. Clinicians, caregivers, and patients should use a shared decision-making process that accounts for patients' values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.
| S-EPMC6561114 | biostudies-literature
Project description:ObjectiveTo develop treatment recommendations for children with juvenile idiopathic arthritis manifesting as non-systemic polyarthritis, sacroiliitis, or enthesitis.MethodsThe Patient/Population, Intervention, Comparison, and Outcomes (PICO) questions were developed and refined by members of the guideline development teams. A systematic review was conducted to compile evidence for the benefits and harms associated with treatments for these conditions. GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology was used to rate the quality of evidence. A group consensus process was conducted among the Voting Panel to generate the final recommendations and grade their strength. A Parent and Patient Panel used a similar consensus approach to provide patient/caregiver preferences for key questions.ResultsThirty-nine recommendations were developed (8 strong and 31 conditional). The quality of supporting evidence was very low or low for 90% of the recommendations. Recommendations are provided for the use of nonsteroidal antiinflammatory drugs, disease-modifying antirheumatic drugs, biologics, and intraarticular and oral glucocorticoids. Recommendations for the use of physical and occupational therapy are also provided. Specific recommendations for polyarthritis address general medication use, initial and subsequent treatment, and adjunctive therapies. Good disease control, with therapeutic escalation to achieve low disease activity, was recommended. The sacroiliitis and enthesitis recommendations primarily address initial therapy and adjunctive therapies.ConclusionThis guideline provides direction for clinicians, caregivers, and patients making treatment decisions. Clinicians, caregivers, and patients should use a shared decision-making process that accounts for patients' values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.
| S-EPMC6561125 | biostudies-literature
Project description:To describe recent evidence from the literature pertaining to juvenile idiopathic arthritis (JIA)-associated uveitis.Uveitis is most common in extended oligoarticular JIA. A significant number of patients already have ocular complications at time of diagnosis of uveitis. Risk factors for complications include either abnormally high or low intraocular pressure, posterior synechiae, male sex, temporal proximity to diagnosis of arthritis and topical corticosteroid use. Use of immunosuppressive agents significantly reduces ocular complications. Aggressive perioperative control of intraocular inflammation is necessary for successful cataract surgery with lens implantation. Controlled clinical trials are under way to assess the efficacy of biologic agents in JIA-associated uveitis. Long-term safety, however, is still unknown.JIA-associated uveitis carries significant ocular morbidity that lasts well into adulthood. Treatment with immunosuppressive agents can reduce the risk of ocular complications. Biologic agents hold promise in the treatment of JIA-associated uveitis, but require long-term data to assess their safety.
| S-EPMC3089768 | biostudies-literature
Project description:Juvenile idiopathic arthritis (JIA) is the most common childhood rheumatic disease. The development of associated uveitis represents a significant risk for serious complications, including permanent loss of vision. Initiation of early treatment is important for controlling JIA-uveitis, but the disease can appear asymptomatically, making frequent screening procedures necessary for patients at risk. As our understanding of pathogenic drivers is currently incomplete, it is difficult to assess which JIA patients are at risk of developing uveitis. Identification of specific risk factors for JIA-associated uveitis is an important field of research, and in this review, we highlight the genomic, transcriptomic, and proteomic factors identified as potential uveitis risk factors in JIA, and discuss therapeutic strategies.
| S-EPMC8393258 | biostudies-literature
Project description:BackgroundHaptoglobin (Hp), a liver derived acute phase inflammatory protein (APP), has scarcely been studied in juvenile idiopathic arthritis (JIA). Hp can occur in blood as two isoforms (Hp1 and Hp2) in precursor and mature forms. Routine clinical chemistry immunoturbidimetry does not discern these forms. It is unknown how different forms relate to disease activity in JIA. Our aims were to determine allele frequency and plasma concentrations of different Hp forms at higher versus lower JIA disease activity and compare to other APPs.MethodsPlasma from JIA (n = 77) and healthy (n = 42) children were analyzed for apparent Hp allelic frequency and densitometric concentrations of alpha forms by Western blot (WB). Polymerase chain reaction (PCR) (buffy coat) was performed in a subset to estimate conformity with genetics. At higher versus lower juvenile arthritis disease activity score (JADAS27) (which includes erythrocyte sedimentation rate (ESR)), total mature Hp concentration from WB was compared and correlated against immunoturbidimetry and total protein, albumin, serum amyloid A (SAA) and C-reactive protein (CRP).ResultsAt 300-fold dilution needed to study mature forms in Western blot, precursors were undetectable. Hp2 contributed most signal in most samples. Hp allele frequency was similar in JIA and controls. Both mature forms, taken separately or by sum, declined following treatment, but remained above concentrations of healthy controls, even in a remission subset that achieved JADAS27 < 1. Densitometry correlated with immunoturbidimetry. Hp concentrations correlated with JADAS27, albumin (negatively), CRP and SAA with immunoturbidimetric method correlating strongest to JADAS27 (Spearman R ~ 0.6, p < 0.0001).ConclusionHp allele frequency in JIA is similar to the general population, indicating that children with JIA should have the same possibility as in healthy children to produce preHp2 (zonulin), thought to increase intestinal permeability. Circulating Hp concentrations largely parallel other APPs and ESR; none of these measures correlate very strongly to JADAS27 score but Hp can be measured from capillary sampling which is impossible with ESR.
| S-EPMC9753416 | biostudies-literature