Alternative titles; symbols
ORPHA: 85414; DO: 676;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 7p15.3 | {Rheumatoid arthritis, systemic juvenile} | 604302 | 3 | IL6 | 147620 | |
| 22q11.23 | {Rheumatoid arthritis, systemic juvenile, susceptibility to} | 604302 | 3 | MIF | 153620 |
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.
Systemic 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.
Fishman 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.
De Benedetti, F., Meazza, C., Vivarelli, M., Rossi, F., Pistorio, A., Lamb, R., Lunt, M., Thomson, W., the British Paediatric Rheumatology Study Group, Ravelli, A., Donn, R., Martini, A. Functional and prognostic relevance of the -173 polymorphism of the macrophage migration inhibitory factor gene in systemic-onset juvenile idiopathic arthritis. Arthritis Rheum. 48: 1398-1407, 2003. [PubMed: 12746913] [Full Text: https://doi.org/10.1002/art.10882]
Donn, R., Alourfi, Z., De Benedetti, F., Meazza, C., Zeggini, E., Lunt, M., Stevens, A., Shelley, E., Lamb, R., the British Paediatric Rheumatology Study Group, Ollier, W. E. R., Thomson, W., Ray, D. Mutation screening of the macrophage migration inhibitory factor gene: positive association of a functional polymorphism of macrophage migration inhibitory factor with juvenile idiopathic arthritis. Arthritis Rheum. 46: 2402-2409, 2002. [PubMed: 12355488] [Full Text: https://doi.org/10.1002/art.10492]
Donn, R. P., Shelley, E., Ollier, W. E. R., Thomson, W., the British Paediatric Rheumatology Study Group. A novel 5-prime-flanking region polymorphism of macrophage migration inhibitory factor is associated with systemic-onset juvenile idiopathic arthritis. Arthritis Rheum. 44: 1782-1785, 2001. [PubMed: 11508429] [Full Text: https://doi.org/10.1002/1529-0131(200108)44:8<1782::AID-ART314>3.0.CO;2-#]
Fishman, D., Faulds, G., Jeffery, R., Mohamed-Ali, V., Yudkin, J. S., Humphries, S., Woo, P. The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis. J. Clin. Invest. 102: 1369-1376, 1998. [PubMed: 9769329] [Full Text: https://doi.org/10.1172/JCI2629]
Glass, D. N., Giannini, E. H. Juvenile rheumatoid arthritis as a complex genetic trait. Arthritis Rheum. 42: 2261-2268, 1999. [PubMed: 10555018] [Full Text: https://doi.org/10.1002/1529-0131(199911)42:11<2261::AID-ANR1>3.0.CO;2-P]
Rooney, M., David, J., Symons, J., Di Giovine, F., Varsani, H., Woo, P. Inflammatory cytokine responses in juvenile chronic arthritis. Brit. J. Rheum. 34: 454-460, 1995. [PubMed: 7788176] [Full Text: https://doi.org/10.1093/rheumatology/34.5.454]
Symmons, D. P., Jones, M., Osborne, J., Sills, J., Southwood, T. R., Woo, P. Pediatric rheumatology in the United Kingdom: data from the British Pediatric Rheumatology Group National Diagnostic Register. J. Rheum. 23: 1975-1980, 1996. [PubMed: 8923378]
Thorne, J. E., Woreta, F., Kedhar, S. R., Dunn, J. P., Jabs, D. A. Juvenile idiopathic arthritis-associated uveitis: incidence of ocular complications and visual acuity loss. Am. J. Ophthal. 143: 840-846, 2007. [PubMed: 17362866] [Full Text: https://doi.org/10.1016/j.ajo.2007.01.033]
Wallace, C. A., Levinson, J. E. Juvenile rheumatoid arthritis: outcome and treatment for the 1990s. Rheum. Dis. Clin. North Am. 17: 891-905, 1991. [PubMed: 1767079]