We searched PubMed for papers with the search terms “juvenile arthritis”, “systemic”, “polyarticular”, “oligoarticular”, “psoriasis”, “spondylarthropathy”, “therapy”, “pathogenesis”, “immunology”, “genetics”, “cytokines”, and “T cells”. We gave preference to papers published between 2005 and 2010, without excluding key references from earlier years. We also gave preference to original studies published in peer-reviewed journals, but also searched for, and if appropriate included,
SeriesJuvenile idiopathic arthritis
Introduction
Juvenile idiopathic arthritis is not a single disease, but a term that encompasses all forms of arthritis that begin before a patient is aged 16 years that persist for more than 6 weeks and are of unknown origin.1, 2 It is the most common childhood chronic rheumatic disease and causes much disability. In high-income countries it has a yearly incidence of 2–20 cases per 100 000 population and a prevalence of 16–150 cases per 100 000 population.1 In this Seminar we focus on developments in the understanding of pathogenesis and in the diagnosis and treatment, and discuss how translational research and new imaging modalities and biomarkers are expected to improve diagnostic and treatment options.
Section snippets
Clinical manifestation and classification
Disorders described by the term juvenile idiopathic arthritis have been grouped on the basis of clinical and laboratory features to try and identify homogeneous, mutually exclusives categories.3 Clinical and laboratory findings have improved the understanding of the different forms of chronic childhood arthritis.4, 5, 6 Although some categories identify definite disease entities, others still include heterogeneous disorders.7
Perspectives for a new classification
To improve our understanding of the cause and development of the various forms of childhood chronic arthritis and find more suitable treatments, the identification of categories that, at least from a clinical point of view, seem as homogeneous as possible is essential to enable immunological, gene expression, and genome-wide association studies. If more homogeneous groups within juvenile idiopathic arthritis are to be identified, which seems likely in view of the heterogeneity within the
Cause and pathogenesis
One of the most intriguing questions in the study of human autoimmune diseases is what determines the phenotype and organ specificity of a disease. In juvenile idiopathic arthritis, for example, the occurrence of uveitis is related to explicit risk factors, such as age at disease onset, sex, the presence of ANA auto-antibodies, and the subtype of juvenile idiopathic arthritis.28, 29, 30 Despite these associations, the immune pathogenesis underlying the link between arthritis and uveitis is
Imaging
Imaging has not been used to its full potential in childhood arthritis.97, 98, 99 Findings from studies in adults are not applicable to children because of the unique features of the growing skeleton, such as age-related variations in the thickness of the articular cartilage, incomplete ossification, and bone growth anomalies induced by the disease. Indeed, for conventional radiology, scoring systems specific for juvenile idiopathic arthritis has been devised.100, 101, 102
As well as being
Treatment
The management of juvenile idiopathic arthritis is based on a combination of pharmacological interventions, physical and occupational therapy, and psychosocial support. Until a decade ago, very few randomised controlled trials (RCT) were done in children with this disease. This situation changed completely with the implementation of the so-called paediatric rule by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA). According to this rule, a company that wishes to
Future perspectives
Major advances during the past 5 years have led to a novel outlook for the care of patients with juvenile idiopathic arthritis. Thanks to pivotal genetic and molecular-immunology studies, immune pathogenesis can be much better linked with clinical phenotypes of disease, which should led to a revision of the original disease classification criteria. Moreover, these studies have led to novel treatment strategies for systemic juvenile idiopathic arthritis and the identification of immune
Search strategy and selection criteria
References (137)
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Juvenile idiopathic arthritis
Lancet
(2007) - et al.
Using biology of disease to understand and guide therapy of JIA
Best Pract Res Clin Rheumatol
(2009) - et al.
Efficacy and safety of tocilizumab in patients with systemic-onset juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled, withdrawal phase III trial
Lancet
(2008) - et al.
Risk of new-onset uveitis in patients with juvenile idiopathic arthritis treated with anti-TNFalpha agents
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Tolerogenic immune responses to novel T-cell epitopes from heat-shock protein 60 in juvenile idiopathic arthritis
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Best Pract Res Clin Rheumatol
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Radiologic investigation of rheumatic diseases
Rheum Dis Clin North Am
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Juvenile idiopathic arthritis: state of the art and future perspectives
Ann Rheum Dis
International league of associations for rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001
J Rheumatol
Th17 and regulatory T cells: rebalancing pro- and anti-inflammatory forces in autoimmune arthritis
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New insights in systemic juvenile idiopathic arthritis—from pathophysiology to treatment
Rheumatology (Oxford)
Heterogeneity in JIA, impact of molecular profiling based on DNA polymorphism and gene expression patterns
Arthritis Rheum
Horror autoinflammaticus: the molecular pathophysiology of autoinflammatory disease (*)
Annu Rev Immunol
Is systemic juvenile rheumatoid arthritis an interleukin 6 mediated disease?
J Rheumatol
Efficacy and safety of tocilizumab in patients with systemic juvenile idiopathic arthritis (sJIA): 12-week data from the phase 3 tender trial
Ann Rheum Dis
Role of interleukin-1 (IL-1) in the pathogenesis of systemic onset juvenile idiopathic arthritis and clinical response to IL-1 blockade
J Exp Med
The pattern of response to anti-interleukin-1 treatment distinguishes two subsets of patients with systemic-onset juvenile idiopathic arthritis
Arthritis Rheum
Anti-cyclic citrullinated peptide (anti-CCP) antibodies in children with juvenile idiopathic arthritis
J Rheumatol
Classification of juvenile spondyloarthritis: enthesitis-related arthritis and beyond
Nat Rev Rheumatol
Are the number of joints involved or the presence of psoriasis still useful tools to identify homogeneous disease entities in juvenile idiopathic arthritis?
J Rheumatol
Patients with antinuclear antibody-positive juvenile idiopathic arthritis constitute a homogeneous subgroup irrespective of the course of joint disease
Arthritis Rheum
Antinuclear antibody positive patients should be grouped as a separate category in the classification of juvenile idiopathic arthritis
Arthritis Rheum
Psoriatic arthritis in children
Arthritis Rheum
Comparison of Vancouver and International League of Associations for rheumatology classification criteria for juvenile psoriatic arthritis
Arthritis Rheum
Patients with juvenile psoriatic arthritis comprise two distinct populations
Arthritis Rheum
Gene expression signatures in polyarticular juvenile idiopathic arthritis demonstrate disease heterogeneity and offer a molecular classification of disease subsets
Arthritis Rheum
Biological similarities based on age at onset in oligoarticular and polyarticular subtypes of juvenile idiopathic arthritis
Arthritis Rheum
Lymphoid neogenesis in juvenile idiopathic arthritis correlates with ANA positivity and plasma cells infiltration
Rheumatology (Oxford)
Juvenile idiopathic arthritis and HLA class I and class II interactions and age-at-onset effects
Arthritis Rheum
Comparison of clinical versus ultrasound-determined synovitis in juvenile idiopathic arthritis
Arthritis Rheum
Ankle disease in juvenile idiopathic arthritis: ultrasound findings in clinically swollen ankles
J Rheumatol
Risk factors for development of uveitis differ between girls and boys with juvenile idiopathic arthritis
Arthritis Rheum
Prevalence, risk factors, and outcome of uveitis in juvenile idiopathic arthritis: a long-term followup study
Arthritis Rheum
Juvenile rheumatoid arthritis as a complex genetic trait
Arthritis Rheum
Twins concordant for juvenile rheumatoid arthritis
Arthritis Rheum
Juvenile rheumatoid arthritis: linkage to HLA demonstrated by allele sharing in affected sibpairs
Arthritis Rheum
A comprehensive review of the genetics of juvenile idiopathic arthritis
Pediatr Rheumatol Online J
Genetics of juvenile idiopathic arthritis: an update
Curr Opin Rheumatol
Non-HLA gene polymorphisms in juvenile rheumatoid arthritis
Clin Exp Rheumatol
A genome-wide scan for juvenile rheumatoid arthritis in affected sibpair families provides evidence of linkage
Arthritis Rheum
Novel IL10 gene family associations with systemic juvenile idiopathic arthritis
Arthritis Res Ther
Specific gene expression profiles in systemic juvenile idiopathic arthritis
Arthritis Rheum
Subtype-specific peripheral blood gene expression profiles in recent-onset juvenile idiopathic arthritis
Arthritis Rheum
Biologic predictors of extension of oligoarticular juvenile idiopathic arthritis as determined from synovial fluid cellular composition and gene expression
Arthritis Rheum
Gene expression profiling of peripheral blood from patients with untreated new-onset systemic juvenile idiopathic arthritis reveals molecular heterogeneity that may predict macrophage activation syndrome
Arthritis Rheum
The meaning of clinical remission in polyarticular juvenile idiopathic arthritis: gene expression profiling in peripheral blood mononuclear cells identifies distinct disease states
Arthritis Rheum
Juvenile arthritis–who gets it, where and when? A review of current data on incidence and prevalence
Clin Exp Rheumatol
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