Juvenile Idiopathic Arthritis

Alexis Boneparth, Norman T Ilowite
US Musculoskeletal Review, 2011;6(1):25-31
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Abstract

Juvenile idiopathic arthritis (JIA) is an umbrella term referring to a clinically heterogeneous group of chronic idiopathic arthritides in children. The most recent JIA classification system, proposed by the International League of Associations for Rheumatology, defines seven categories of disease each with distinct clinical features. Disease pathogenesis is poorly understood, but is thought to be multifactorial, including both genetic and environmental factors. Disease morbidity includes both intra-articular and extra-articular manifestations, and the goal of treatment should be complete remission of disease activity. There is no cure for JIA, but recent advances in pharmacotherapy have greatly expanded treatment options and improved outcomes. More work is needed to elucidate disease pathogenesis and thereby promote the development of additional targeted therapies.
Keywords
Juvenile idiopathic arthritis, etiology, prognosis, treatment
Disclosure The authors have no conflicts of interest to declare.
Received: January 18, 2011 Accepted April 20, 2011
Correspondence: Norman T Ilowite, MD, Division of Pediatric Rheumatology, The Children’s Hospital at Montefiore, 3415 Bainbridge Avenue, Bronx, NY 10467. E: NIlowite@montefiore.org

Juvenile idiopathic arthritis (JIA) is a broad umbrella term referring to a group of related disorders. JIA is a clinical diagnosis made in a child under 16 years old with arthritis of at least six weeks’ duration, with other identifiable causes of arthritis excluded. JIA is the most common chronic rheumatic disease in children and is a significant cause of short- and long-term disability.

Different classification systems have been used to define JIA subtypes. The most recent system was proposed in 1993 and revised in 2004 by the International League of Associations for Rheumatology (ILAR).1 It classifies JIA as including seven categories: systemic, oligoarticular, polyarticular rheumatoid factor (RF)-positive, polyarticular RF-negative, enthesitis-related arthritis (ERA), juvenile psoriatic arthritis (JPsA) and undifferentiated arthritis. The aim of this classification system is to define relatively homogenous and mutually exclusive categories of disease to facilitate communication regarding epidemiology, therapeutics and outcomes among physicians globally. No classification system has been perfect, and many patients will be classified in this schema as being undifferentiated because they satisfy criteria for none or more than one category. It is expected that, as new insights into the pathogenesis of JIA emerge, further refinements in disease classification will be possible.

Epidemiology
The reported incidence and prevalence of JIA vary considerably throughout the world and in different studies. The incidence of JIA ranges from 1 to 22 per 100,0002,3 with a prevalence of 8–400 per 100,000.4,5 When compared with referral- or clinic-based surveys, community-based studies exhibit considerably higher prevalence estimates,5,6 suggesting that a substantial number of children with chronic arthritis are not referred for rheumatologic evaluation. In Europe and North America, oligoarthritis is the most common subtype, accounting for approximately 50% of patients. RF-positive polyarthritis is the least common subtype, accounting for 5–10% of patients. In most of the Western world, girls are affected more often than boys, although different subtypes vary in this regard. ERA affects males more than it does females, whereas systemic onset JIA (SJIA) affects both equally.

Etiology and Pathophysiology
The pathogenesis of JIA is not well understood. It is probably multifactorial, and both genetic and environmental factors are thought to contribute. Some hypothesize that the disease is triggered in a genetically predisposed individual by infection, abnormal hormone levels, joint trauma, or psychological stress. Narrow peak ages of onset for certain subtypes suggest that age, prior antigenic experience and immunologic maturity also have a role. Several studies have suggested parvovirus B19 as a possible cause of chronic arthritis in children.7,8 Chronic arthritis has also been described in children with HIV infection.9 Immune response to highly conserved bacterial heat shock proteins has been linked to disease activity, suggesting a role for molecular mimicry in disease onset.10 Numerous human leukocyte antigen (HLA) class I and class II allele associations have been described in JIA. These associations have been shown to vary by JIA subtype and have been reviewed extensively elsewhere.11 The class I antigen HLA-A2 and class II antigens DRB1*08 and DQA1*04 are associated with early-onset oligoarticular arthritis as well as with RF-negative polyarticular disease, suggesting pathogenic similarity between these subtypes.11–14 HLA DRB1*04 and DRB1*07 are seen less frequently in children with oligoarticular JIA compared with controls, suggesting that these alleles are protective.15–17 HLA-DRB1*04, which is associated with adult rheumatoid arthritis, is associated with polyarticular RF-positive JIA.13,14 Early studies suggested HLA allele associations for SJIA, but these findings have not been replicated.13 The class I antigen HLA-B27 and class II antigens HLA-DRB1*01 and DQA1*0101 are associated with ERA and JPsA.13

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