Rheumatoid Arthritis, Systemic Juvenile
A number sign (#) is used with this entry because multiple factors influence the susceptibility to systemic juvenile rheumatoid arthritis. Polymorphisms in the IL6 (147620.0001) and in the MIF gene (153620.0001) have been found to be associated with susceptibility to the disorder.
Glass and Giannini (1999) reviewed juvenile rheumatoid arthritis as a complex genetic trait.
Clinical FeaturesSystemic juvenile rheumatoid arthritis is a subset of juvenile chronic, or idiopathic, arthritis, representing approximately 11% of patients with this disease. The systemic-onset form represents a subgroup most likely to be associated with severe, debilitating, extraarticular features, and occasionally fatal complications. Despite medical treatment, many children still experience early joint destruction, necessitating surgical replacement. Moreover, up to 48% of these patients still have active disease after 10 years (Wallace and Levinson, 1991).
Systemic juvenile rheumatoid arthritis is a clinically homogeneous disease. During active phases of the disorder, patients display a typical 'quotidian' (daily) spiking fever, an evanescent macular rash, lymphadenopathy, hepatosplenomegaly, serositis, myalgia, and arthritis. They are frequently anemic with markedly elevated neutrophil and platelet counts; they have a high erythrocyte sedimentation rate, C-reactive protein, and serum fibrinogen. The particularly unusual feature of acute systemic juvenile rheumatoid arthritis is the unique pattern of fever. Rooney et al. (1995) found that interleukin-6 (IL6; 147620) concentration rises significantly in conjunction with the fever spike, and then falls in parallel with the return of body temperature to normal.
Thorne et al. (2007) stated that uveitis is reported to occur in about 30% of patients with juvenile idiopathic arthritis (JIA) who are antinuclear antibody-positive regardless of the type of arthritis present. The uveitis in these patients is typically a chronic, bilateral, nongranulomatous, and asymptomatic anterior uveitis. In a retrospective analysis of 75 patients with JIA-associated uveitis, Thorne et al. (2007) found that incident vision loss and complications were common. Active inflammation during follow-up was associated with increased risk of visual impairment, but use of immunosuppressive drugs appeared to reduce the risk.
Molecular GeneticsFishman et al. (1998) found a relationship between a polymorphism of IL6 (147620.0001) and systemic juvenile rheumatoid arthritis.
Donn et al. (2001) identified a G-to-C transition at position -173 of the MIF gene (153620.0001) and screened for this polymorphism in 117 patients with systemic juvenile rheumatoid arthritis and 172 unrelated healthy controls. They found that individuals possessing the MIF-173C allele had an increased risk of the disease (p = 0.0005). Donn et al. (2002) screened for the MIF-173C allele in a group of 88 patients with juvenile rheumatoid arthritis of varying clinical phenotypes. They confirmed the increased risk of susceptibility to juvenile rheumatoid arthritis and also found that the increased risk was not limited to any one clinical subgroup. De Benedetti et al. (2003) studied 136 patients with systemic juvenile rheumatoid arthritis and found that the MIF-173C allele was associated with higher serum and synovial fluid levels of MIF, poorer response to glucocorticoid treatment, persistence of active disease, and a poor functional outcome.
For discussion of a possible association between systemic juvenile rheumatoid arthritis and variation in the LACC1 gene on chromosome 13q14, see 613409.0001.