Juvenile idiopathic arthritis (JIA) is the most common paediatric rheumatological disorder and is classified by subtype according to International League of Associations for Rheumatology criteria. ...Depending on the number of joints affected, presence of extra-articular manifestations, systemic symptoms, serology and genetic factors, JIA is divided into oligoarticular, polyarticular, systemic, psoriatic, enthesitis-related and undifferentiated arthritis. This review provides an overview of advances in understanding of JIA pathogenesis focusing on aetiology, histopathology, immunological changes associated with disease activity, and best treatment options. Greater understanding of JIA as a collective of complex inflammatory diseases is discussed within the context of therapeutic interventions, including traditional non-biologic and up-to-date biologic disease-modifying anti-rheumatic drugs. Whilst the advent of advanced therapeutics has improved clinical outcomes, a considerable number of patients remain unresponsive to treatment, emphasising the need for further understanding of disease progression and remission to support stratification of patients to treatment pathways.
Patients with JIA, specifically the polyarticular subtype, may present with temporomandibular joint arthritis. Given the pain typically present in the joint, limitations in opening may be noted. As ...such, oral health and hygiene practices may be compromised in this patient population. Dental management considerations during treatment include shorter visits, safe measures to maintain mouth opening, frequent breaks during procedures, and counselling on condition management to reduce risks in the future. In dental extractions, bite blocks or props may be used to complete the procedure safely and reduce pain.
To revise the current juvenile idiopathic arthritis (JIA) International League of Associations for Rheumatology (ILAR) classification criteria with an evidence-based approach, using clinical and ...routine laboratory measures available worldwide, to identify homogeneous clinical groups and to distinguish those forms of chronic arthritis typically seen only in children from the childhood counterpart of adult diseases.
The overall project consists of 4 steps. This work represents Step 1, a Delphi Web-based consensus and Step 2, an international nominal group technique (NGT) consensus conference for the new provisional Pediatric Rheumatology International Trials Organization JIA classification criteria. A future large data collection of at least 1000 new-onset JIA patients (Step 3) followed by analysis and NGT consensus (Step 4) will provide data for the evidence-based validation of the JIA classification criteria.
In Step 1, three Delphi rounds of interactions were implemented to revise the 7 ILAR JIA categories. In Step 2, forty-seven questions with electronic voting were implemented to derive the new proposed criteria. Four disorders were proposed: (a) systemic JIA; (b) rheumatoid factor-positive JIA; (c) enthesitis/spondylitis-related JIA; and (d) early-onset antinuclear antibody-positive JIA. The other forms were gathered under the term "others." These will be analyzed during the prospective data collection using a list of descriptors to see whether the clustering of some of them could identify homogeneous entities.
An international consensus was reached to identify different proposed homogeneous chronic disorders that fall under the historical term
. These preliminary criteria will be formally validated with a dedicated project.
Juvenile idiopathic arthritis remains one of the most common chronic inflammatory rheumatic diseases of childhood. A significant proportion of patients experience nausea, vomiting, abdominal pain and ...loss of appetite with methotrexate therapy, which can significantly complicate the course of the disease.
The aim was to study the clinical and anamnestic signs of liver disorders in children, depending on the manifestations of juvenile idiopathic arthritis.
Materials and methods of research. The presence of gastrointestinal complaints, namely abdominal pain, loss of appetite, nausea and vomiting in 104 children with juvenile idiopathic arthritis who were treated at the State Institution "Institute of Child and Adolescent Health of the National Academy of Medical Sciences of Ukraine" was analyzed.
Results. According to the results of the study, children with juvenile idiopathic arthritis had gastrointestinal complaints in 47.12%. We find out that the majority of children had gastrointestinal complains at the age of 10–13 years (55.36%, p ˂ 0.001), and at the onset of the disease after 15 years (100%, p ˂ 0.01). Young children often complained of abdominal pain and vomiting, older children complained of loss of appetite and persistent nausea, regardless of the variant, activity, duration of arthritis and the presence of methotrexate in complex therapy. It was also found that appearance of gastrointestinal complaints were observed more often at a dose of methotrexate less than 10 mg / m2 / body surface (p ˂ 0.05).
Conclusions. 1. We find out that in 47.12% children with juvenile idiopathic arthritis had gastrointestinal complaints, aged 10–13 years (55.36%; p ˂ 0.001). The most amounts of complaints were common for patients older than 15 years old (p ˂ 0.01). 2. The nature of the complaints varied and depended mainly on the age of the patients. Younger children had abdominal pain and vomiting simultaneously older children had decreased appetite and nausea. The presence of complaints did not depend on the variant, activity and duration of the juvenile idiopathic arthritis. 3. According to our study complaints were not due to the presence of methotrexate in combination therapy. Children complained much more often if methotrexate dose was less than 10 mg / m2 than in the case of higher doses (p ˂ 0.05).
Juvenile idiopathic arthritis (JIA) is a complex rheumatic disease with both autoimmune and autoinflammatory components. Recently, familial cases of systemic-onset JIA have been attributed to ...mutations in LACC1/FAMIN. We describe three affected siblings from a Moroccan consanguineous family with an early-onset chronic, symmetric and erosive arthritis previously diagnosed as rheumatoid factor (RF)-negative polyarticular JIA. Autozygosity mapping identified four homozygous regions shared by all patients, located in chromosomes 3, 6 (n:2) and 13, containing over 330 genes. Subsequent whole exome sequencing identified two potential candidate variants within these regions (in FARS2 and LACC1/FAMIN). Genotyping of a cohort of healthy Moroccan individuals (n: 352) and bioinformatics analyses finally supported the frameshift c.128_129delGT mutation in the LACC1/FAMIN gene, leading to a truncated protein (p.Cys43Tyrfs*6), as the most probable causative gene defect. Additional targeted sequencing studies performed in patients with systemic-onset JIA (n:23) and RF-negative polyarticular JIA (n: 44) revealed no pathogenic LACC1/FAMIN mutations. Our findings support the homozygous genotype in the LACC1/FAMIN gene as the defect underlying the family here described with a recessively inherited severe inflammatory joint disease. Our evidences provide further support to the involvement of LACC1/FAMIN deficiency in different types of JIA in addition to the initially described systemic-onset JIA.
This work has been partially funded by: CERCA Programme/Generalitat de Catalunya (JIA, XE, SO), the PERIS program of the Generalitat de Catalunya grant SLT002/16/00310 (RR), the Spanish Ministry of Economy and Competitiveness co-financed by European Regional Development Fund (ERDF) grant SAF2015-68472-C2-1-R (JIA), the Instituto de Salud Carlos III/Transnational Research Projects on Rare Diseases (JIA) grant AC15/00027, the Spanish Society of Pediatric Rheumatology (JIA), the Secretaria d’Universitats i Recerca del Departament d’Economia grant 2009-SGR-1502 (XE) and the European Union Seventh Framework Programme (FP7/2007-2013) grant agreement no. 262055 (XE).
Systemic Juvenile Idiopathic Arthritis Lee, Jennifer J Y; Schneider, Rayfel
The Pediatric clinics of North America,
08/2018, Volume:
65, Issue:
4
Journal Article
Peer reviewed
Systemic juvenile idiopathic arthritis (sJIA) is a distinctive subtype of juvenile idiopathic arthritis, characterized by fever and arthritis, often accompanied by rash, sometimes by generalized ...lymphadenopathy, hepatosplenomegaly, and serositis. The diagnosis requires adequate exclusion of infectious, oncologic, autoimmune, and autoinflammatory diseases. Macrophage activation syndrome, a serious and potentially fatal complication of sJIA, requires prompt evaluation and treatment. Newer biologic agents, particularly interleukin-1 and interleukin-6 inhibitors, are highly effective and have transformed the treatment approach by reducing the use of systemic glucocorticoids. Primary care providers have a crucial role in monitoring children with sJIA for disease-related complications and medication-related adverse events.
Abstract
Objective
To compare clinical features and treatments of patients with systemic JIA (sIJA) and adult-onset Still’s disease (AOSD).
Methods
The clinical charts of consecutive patients with ...sJIA by International League of Association of Rheumatology criteria or AOSD by Yamaguchi criteria were reviewed. Patients were seen at a large paediatric rheumatology referral centre or at 10 adult rheumatology academic centres. Data collected included clinical manifestations, inflammation biomarkers, systemic score, macrophage activation syndrome (MAS), parenchymal lung disease, disease course, disability, death and medications administered.
Results
A total of 166 patients (median age at diagnosis 5 years) with sJIA and 194 patients with AOSD (median age at diagnosis 41 years) were included. The frequency of fever, rash, arthralgia, abdominal pain, MAS, parenchymal lung disease and increased acute phase reactants and ferritin were comparable between the two cohorts. Patients with sJIA had a higher prevalence of arthritis, whereas patients with AOSD had experienced leucocytosis and extra-articular organ involvement more frequently. Patients with AOSD were given more commonly low-dose corticosteroids, whereas biologic DMARDs were administered first-line more frequently in patients with sJIA.
Conclusion
We found remarkable disparities in the prevalence of clinical manifestations between the two illnesses, which may partly depend on their classification by different criteria.
Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic condition in childhood. The disease etiology remains largely unknown; however, a key role in JIA pathogenesis is surely ...mediated by T cells. T‐lymphocytes activity is controlled via signals, known as immune checkpoints. Delivering an inhibitory signal or blocking a stimulatory signal to achieve immune suppression is critical in autoimmune diseases. However, the role of immune checkpoints in chronic inflammation and autoimmunity must still be deciphered. In this study, we investigated at the single‐cell level the feature of T cells in JIA chronic inflammation, both at the transcriptome level via single‐cell RNA sequencing and at the protein level by flow cytometry. We found that despite the heterogeneity in the composition of synovial CD4+ and CD8+ T cells, those characterized by PD‐1 expression were clonally expanded tissue‐resident memory (Trm)‐like cells and displayed the highest proinflammatory capacity, suggesting their active contribution in sustaining chronic inflammation in situ. Our data support the concept that novel therapeutic strategies targeting PD‐1 may be effective in the treatment of JIA. With this approach, it may become possible to target overactive T cells regardless of their cytokine production profile.
T cells expressing PD‐1 are enriched in synovial fluid of juvenile idiopathic arthritis patients. Interestingly, PD‐1 positive cells exhibit markers of tissue residency, display a high proinflammatory capacity, and are clonally expanded cells, suggesting their active contribution in sustaining chronic inflammation in situ.
PDF
