Clinical and Experimental Pediatrics

The Korean Pediatric Society (대한소아청소년과학회)
권호 표지
DOI QR코드

DOI QR Code

Pathogenesis and clinical manifestations of juvenile rheumatoid arthritis

  • Hahn, Youn-Soo (Department of Pediatrics, Chungbuk National University College of Medicine) ;
  • Kim, Joong-Gon (Department of Pediatrics, Seoul National University College of Medicine)
  • Received : 2010.10.04
  • Accepted : 2010.10.19
  • Published : 2010.11.15
Download PDF
⟨ Previous Next ⟩

Abstract

Juvenile rheumatoid arthritis (JRA) is the most common rheumatic childhood disease; its onset is before 16 years of age and it persists for at least 6 weeks. JRA encompasses a heterogeneous group of diseases that is classified according to 3 major presentations: oligoarthritis, polyarthritis, and systemic onset diseases. These presentations may originate from the same or different causes that involve interaction with specific immunogenetic predispositions, and result in heterogeneous clinical manifestations. An arthritic joint exhibits cardinal signs of joint inflammation, such as swelling, pain, heat, and loss of function; any joint can be arthritic, but large joints are more frequently affected. Extra-articular manifestations include high fever, skin rash, serositis, and uveitis. The first 2 types of JRA are regarded as T helper 1 (Th1) cell-mediated inflammatory disorders, mainly based on the abundance of activated Th1 cells in the inflamed synovium and the pathogenetic role of proinflammatory cytokines that are mainly produced by Th1 cell-stimulated monocytes. In contrast, the pathogenesis of systemic onset disease differs from that of other types of JRA in several respects, including the lack of association with human leukocyte antigen type and the absence of autoantibodies or autoreactive T cells. Although the precise mechanism that leads to JRA remains unclear, proinflammatory cytokines are thought to be responsible for at least part of the clinical symptoms in all JRA types. The effectiveness of biologic therapy in blocking the action of these cytokines in JRA patients provides strong evidence that they play a fundamental role in JRA inflammation.

Keywords

References

  1. Phelan J, Thompson S. Genomic progress in pediatric arthritis: recent work and future goals. Curr Opin Rheumatol 2006;18:482-9. https://doi.org/10.1097/01.bor.0000240359.30303.e4
  2. Forre O, Smerdel A. Genetic epidemiology of juvenile idiopathic arthritis. Scand J Rheumatol 2002;31:123-8. https://doi.org/10.1080/rhe.31.3.123.128
  3. Murray K, Thompson SD, Glass DN. Pathogenesis of juvenile chronic arthritis: genetic and environmental factors. Arch Dis Child 1997;77:530-4. https://doi.org/10.1136/adc.77.6.530
  4. Adams A, Lehman TJ. Update on the pathogenesis and treatment of systemic onset juvenile rheumatoid arthritis. Curr Opin Rheumatol 2005;17:612-6. https://doi.org/10.1097/01.bor.0000169363.69066.d0
  5. Wilkinson N, Jackson G, Gardner-Medwin J. Biologic therapies for juvenile arthritis. Arch Dis Child 2003;88:186-91. https://doi.org/10.1136/adc.88.3.186
  6. Brewer EJ Jr, Bass J, Baum J, Cassidy JT, Fink C, Jacobs J, et al. Current proposed revision of JRA criteria. JRA Criteria Subcommittee of the Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Section of The Arthritis Foundation. Arthritis Rheum 1977;20:195-9.
  7. European League Against Rheumatism. EULAR Bulletin No. 4: nomenclature and classification of arthritis in children. Basel (Switzerland): National Zeitung AG, 1977.
  8. Petty RE, Southwood TR, Baum J, Bhettay E, Glass DN, Manners P, et al. Revision of the proposed classification criteria for juvenile idiopathic arthritis: Durban 1997. J Rheumatol 1998;25:1991-4.
  9. Manners PJ, Bower C. Worldwide prevalence of juvenile arthritis-why does it vary so much? J Rheumatol 2002;29:1520-30.
  10. Fujikawa S, Okuni M. A nationwide surveillance study of rheumatic diseases among Japanese children. Acta Paediatr Jpn 1997;39:242-4. https://doi.org/10.1111/j.1442-200X.1997.tb03592.x
  11. Saurenmann RK, Rose JB, Tyrrell P, Feldman BM, Laxer RM, Schneider R, et al. Epidemiology of juvenile idiopathic arthritis in a multiethnic cohort: ethnicity as a risk factor. Arthritis Rheum 2007;56:1974-84. https://doi.org/10.1002/art.22709
  12. Moroldo MB, Tague BL, Shear ES, Glass DN, Giannini EH. Juvenile rheumatoid arthritis in affected sib-pairs. Arthritis Rheum 1997;40:1962-6. https://doi.org/10.1002/art.1780401107
  13. Glass DN, Giannini EH. Juvenile rheumatoid arthritis as a complex genetic trait. Arthritis Rheum 1999;42:2261-8. https://doi.org/10.1002/1529-0131(199911)42:11<2261::AID-ANR1>3.0.CO;2-P
  14. Prahalad S. Genetics of juvenile idiopathic arthritis: an update. Curr Opin Rheumatol 2004;16:588-94. https://doi.org/10.1097/01.bor.0000134407.48586.b0
  15. Thomson W, Donn R. Juvenile idiopathic arthritis genetics-what's new? What's next? Arthritis Res 2002;4:302-6. https://doi.org/10.1186/ar591
  16. Hinks A, Barton A, John S, Bruce I, Hawkins C, Griffiths CE, et al. Association between the PTPN22 gene and rheumatoid arthritis and juvenile idiopathic arthritis in a UK population: further support that PTPN22 is an autoimmunity gene. Arthritis Rheum 2005;52:1694-9. https://doi.org/10.1002/art.21049
  17. Rosen P, Thompson S, Glass D. Non-HLA gene polymorphisms in juvenile rheumatoid arthritis. Clin Exp Rheumatol 2003;21:650-6.
  18. Wedderburn LR, Robinson N, Patel A, Varsani H, Woo P. Selective recruitment of polarized T cells expressing CCR5 and CXCR3 to the inflamed joints of children with juvenile idiopathic arthritis. Arthritis Rheum 2000;43:765-74. https://doi.org/10.1002/1529-0131(200004)43:4<765::AID-ANR7>3.0.CO;2-B
  19. Gattorno M, Prigione I, Moranti F, Gregorio A, Chiesa S, Ferlito F, et al. Phenotypic and functional characterization of CCR7+ and CCR7- CD4+ memory T cells homing to the joints in juvenile idiopathic arthritis. Arthritis Res Ther 2005;7:R256-67.
  20. Scola MP, Imagawa T, Boivin GP, Glass DN, Hirsch R, Grom AA, et al. Expression of angiogenic factors in juvenile rheumatoid arthritis: correlation with revascularization of human synovium engrafted into SCID mice. Arthritis Rheum 2001;44:794-801. https://doi.org/10.1002/1529-0131(200104)44:4<794::AID-ANR135>3.0.CO;2-7
  21. Gattorno M, Gregorio A, Ferlito F, Gerloni V, Parafioriti A, Felici E, et al. Synovial expression of osteopontin correlates with angiogenesis in juvenile idiopathic arthritis. Rheumatology 2004;43:1091-6. https://doi.org/10.1093/rheumatology/keh250
  22. Grom AA, Murray KJ, Luyrink L, Emery H, Passo MH, Glass DN, et al. Patterns of expression of tumor necrosis factor $\alpha$, tumor necrosis factor $\beta$, and their receptors in synovia of patients with juvenile rheumatoid arthritis and juvenile spondylarthropathy. Arthritis Rheum 1996;39:1703-10. https://doi.org/10.1002/art.1780391013
  23. Kutukculer N, Caglayan S, Aydogdu F. Study of pro-inflammatory ($TNF-\alpha,\;IL-1\alpha,\;IL-6$) and T-cell-derived (IL-2, IL-4) cytokines in plasma and synovial fluid of patients with juvenile chronic arthritis: correlations with clinical and laboratory parameters. Clin Rheumatol 1998;17:288-92. https://doi.org/10.1007/BF01451007
  24. Shingu M, Nagai Y, Isayama T, Naono T, Nobunaga M, Nagai Y. The effects of cytokines on metalloproteinase inhibitors (TIMP) and collagenase production by human chondrocytes and TIMP production by synovial cells and endothelial cells. Clin Exp Immunol 1993;94:145-9.
  25. Keffer J, Probert L, Cazlaris H, Georgopoulos S, Kaslaris E, Kioussis D, et al. Transgenic mice expressing human tumour necrosis factor: a predictive genetic model of arthritis. EMBO J 1991;10:4025-31.
  26. Wooley PH, Dutcher J, Widmer MB, Gillis S. Influence of a recombinant human soluble tumor necrosis factor receptor Fc fusion protein on type II collagen-induced arthritis in mice. J Immunol 1993;151:6602-7.
  27. Williams RO, Feldmann M, Maini RN. Anti-tumor necrosis factor ameliorates joint disease in murine collagen-induced arthritis. Proc Natl Acad Sci U S A 1992;89:9784-8. https://doi.org/10.1073/pnas.89.20.9784
  28. Pettipher ER, Higgs GA, Henderson B. Interleukin 1 induces leukocyte infiltration and cartilage proteoglycan degradation in the synovial joint. Proc Natl Acad Sci U S A 1986;83:8749-53. https://doi.org/10.1073/pnas.83.22.8749
  29. Joosten LAB, Helsen MMA, van de Loo FAJ, van den Berg WB. Anticytokine treatment of established type II collagen-induced arthritis in DBA/1 mice: a comparative study using $anti-TNF{\alpha},\;anti-IL-1{\alpha/\beta}$, and IL-1Ra. Arthritis Rheum 1996;39:797-809. https://doi.org/10.1002/art.1780390513
  30. Nishimoto N, Kishimoto T. Interleukin 6: from bench to bedside. Nat Clin Pract Rheumatol 2006;2:619-26. https://doi.org/10.1038/ncprheum0338
  31. Mangge H, Kenzian H, Gallistl S, Neuwirth G, Liebmann P, Kaulfersch W, et al. Serum cytokines in juvenile rheumatoid arthritis. Correlation with conventional inflammation parameters and clinical subtypes. Arthritis Rheum 1995;38:211-20. https://doi.org/10.1002/art.1780380209
  32. Ou LS, See LC, Wu CJ, Kao CC, Lin YL, Huang JL. Association between serum inflammatory cytokines and disease activity in juvenile idiopathic arthritis. Clin Rheumatol 2002;21:52-6. https://doi.org/10.1007/s100670200012
  33. Heinrich PC, Castell JV, Andus T. Interleukin-6 and the acute phase response. Biochem J. 1990;265:621-36. https://doi.org/10.1042/bj2650621
  34. Weaver CT, Harrington LE, Mangan PR, Gavrieli M, Murphy KM. Th17: an effector of CD4 T cell lineage with regulatory T cell ties. Immunity 2006;24:677-88. https://doi.org/10.1016/j.immuni.2006.06.002
  35. Jovanovic DV, Di Battista JA, Martel-Pelletier J, Jolicoeur FC, He Y, Zhang M, et al. IL-17 stimulates the production and expression of proinflammatory cytokines, $IL-1\beta$ and $TNF-\alpha$, by human macrophages. J Immunol 1998;160:3513-21.
  36. Chabaud M, Fossiez F, Taupin JL, Miossec P. Enhancing effect of IL-17 on IL-1-induced IL-6 and leukemia inhibitory factor production by rheumatoid arthritis synoviocytes and its regulation by Th2 cytokines. J Immunol 1998;161:409-14.
  37. Katz Y, Nadiv O, Beer Y. Interleukin-17 enhances tumor necrosis factor $\alpha$-induced synthesis of interleukins 1, 6, and 8 in skin and synovial fibroblasts: a possible role as a "fine-tuning cytokine" in inflammation processes. Arthritis Rheum 2001;44:2176-84. https://doi.org/10.1002/1529-0131(200109)44:9<2176::AID-ART371>3.0.CO;2-4
  38. Chabaud M, Garnero P, Dayer JM, Guerne PA, Fossiez F, Miossec P. Contribution of interleukin 17 to synovium matrix destruction in rheumatoid arthritis. Cytokine 2000;12:1092-9. https://doi.org/10.1006/cyto.2000.0681
  39. Sato K, Suematsu A, Okamoto K, Yamaguchi A, Morishita Y, Kadono Y, et al. Th17 functions as an osteoclastogenic helper T cells subset that links T cell activation and bone destruction. J Exp Med 2006;203:2673-82. https://doi.org/10.1084/jem.20061775
  40. Kotake S, Udagawa N, Takahashi N, Matsuzaki K, Itoh K, Ishiyama S, et al. IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis. J Clin Invest 1999;103:1345-52. https://doi.org/10.1172/JCI5703
  41. De Jager W, Hoppenreijs EP, Wulffraat NM, Wedderburn LR, Kuis W, Prakken BJ. Blood and synovial fluid cytokine signatures in patients with juvenile idiopathic arthritis: a cross-sectional study. Ann Rheum Dis 2007;66:589-98. https://doi.org/10.1136/ard.2006.061853
  42. Nakae S, Nambu A, Sudo K, Iwakura Y. Suppression of immune induction of collagen-induced arthritis in IL-17-deficient mice. J Immunol 2003;171:6173-7. https://doi.org/10.4049/jimmunol.171.11.6173
  43. Lubberts E, Konders MI, Oppers-Walgreen B, van den Bersselaar L, Coenen-de Roo CJ, Joosten LA, et al. Treatment with a neutalizing anti-murine IL-17 antibody after the onset of collagen-induced arthritis reduces joint inflammation, cartilage destruction and bone erosion. Arthritis Rheum 2004;50:650-9. https://doi.org/10.1002/art.20001
  44. Nepom BS, Glass DN. Juvenile rheumatoid arthritis and HLA: report of the Park City III workshop. J Rheumatol Suppl 1992;33:70-4.
  45. Ravelli A, Martini A. Juvenile idiopathic arthritis. Lancet 2007;369:767-78. https://doi.org/10.1016/S0140-6736(07)60363-8
  46. Frosch M, Metze D, Foell D, Vogl T, Sorg C, Sunderkötter C, et al. Early activation of cutaneous vessels and epithelial cells is characteristic of acute systemic onset juvenile idiopathic arthritis. Exp Dermatol 2005;14:259-65. https://doi.org/10.1111/j.0906-6705.2005.00271.x
  47. Foell D, Roth J. Proinflammatory S100 proteins in arthritis and autoimmune disease. Arthritis Rheum 2004;50:3762-71. https://doi.org/10.1002/art.20631
  48. Frosch M, Vogl T, Seeliger S, Wulffraat N, Kuis W, Viemann D, et al. Expression of myeloid-related proteins 8 and 14 in systemic-onset juvenile rheumatoid arthritis. Arthritis Rheum 2003;48:2622-6. https://doi.org/10.1002/art.11177
  49. Foell D, Wittkowski H, Hammerschmidt I, Wulffraat N, Schmeling H, Frosch M, et al. Monitoring neutrophil activation in juvenile rheumatoid arthritis by S100A12 serum concentrations. Arthritis Rheum 2004;50:1286-95. https://doi.org/10.1002/art.20125
  50. Roth J, Vogl T, Sorg C, Sunderkotter C. Phagocyte specific S100 proteins: a novel group of proinflammatory molecules. Trends Immunol 2003;24:155-8. https://doi.org/10.1016/S1471-4906(03)00062-0
  51. Viemann D, Strey A, Janning A, Jurk K, Klimmek K, Vogl T, et al. Myeloid-related proteins 8 and 14 induce a specific inflammatory response in human microvascular endothelial cells. Blood 2005;105:2955-62. https://doi.org/10.1182/blood-2004-07-2520
  52. Pascual V, Allantaz F, Arce E, Punaro M, Banchereaux J. Role of interleukin (IL-1) in the pathogenesis of systemic onset juvenile idiopathic arthritis and clinical response to IL-1 blockade. J Exp Med 2005;201:1479-86. https://doi.org/10.1084/jem.20050473
  53. Kawaguchi Y, Terajima H, Harigai M, Hara M, Kamatani N. Interleukin- 18 as a novel diagnostic marker and indicator of disease severity in adult-onset Still's disease. Arthritis Rheum 2001;44:1716-7. https://doi.org/10.1002/1529-0131(200107)44:7<1716::AID-ART298>3.0.CO;2-I
  54. Maeno N, Takei S, Nomura Y, Imanaka H, Hokonohara M, Miyata K. Highly elevated serum levels of interleukin-18 in systemic juvenile idiopathic arthritis but not in other juvenile idiopathic arthritis subtypes or in Kawasaki disease: comment on the article by Kawashima et al. Arthritis Rheum 2002;46:2539-41. https://doi.org/10.1002/art.10389
  55. De Benedetti F, Massa M, Robbioni P, Ravelli A, Burgio GR, Martini A. Correlation of serum interleukin-6 levels with joint involvement and thrombocytosis in systemic juvenile rheumatoid arthritis. Arthritis Rheum 1991;34:1158-63. https://doi.org/10.1002/art.1780340912
  56. De Benedetti F, Massa M, Pignatti P, Albani S, Novick D, Martini A. Serum soluble interleukin 6 (IL-6) receptor and IL-6/soluble IL-6 receptor complex in systemic juvenile rheumatoid arthritis. J Clin Invest 1994;93:2114-9. https://doi.org/10.1172/JCI117206
  57. De Benedetti F, Pignatti P, Gerloni V, Massa M, Sartirana P, Caporali R, et al. Differences in synovial fluid cytokine levels between juvenile and adult rheumatoid arthritis. J Rheumatol 1997;24:1403-9.
  58. Cazzola M, Ponchio L, De Benedetti F, Ravelli A, Rosti V, Beguin Y, et al. Defective iron supply to erythropoiesis and adequate endogenous erythropoietin production in the anemia associated with systemic-onset juvenile chronic arthritis. Blood 1996;87:4824-30.
  59. De Benedetti F, Rucci N, Del Fattore A, Peruzzi B, Paro R, Longo M, et al. Impaired skeletal development in interleukin-6-transgenic mice. A model for the impact of chronic inflammation on the growing skeletal system. Arthritis Rheum 2006;54:3551-63. https://doi.org/10.1002/art.22175
  60. Yokota S, Miyamae T, Imagawa T, Iwata N, Katakura S, Mori M, et al. Therapeutic efficacy of humanized recombinant anti-interleukin-6 receptor antibody in children with systemic onset juvenile idiopathic arthritis. Arthritis Rheum 2005;52:818-25. https://doi.org/10.1002/art.20944
  61. Villanueva J, Lee S, Giannini EH, Graham TB, Passo MH, Filipovich A. Natural killer cell dysfunction is a distinguishing feature of systemic onset juvenile rheumatoid arthritis and macrophage activation syndrome. Arthritis Res Ther 2005;7:R30-7. https://doi.org/10.1186/ar1453
  62. Wulffraat NM, Rijkers GT, Elst E, Brooimans R, Kuis W. Reduced perforin expression in systemic juvenile idiopathic arthritis is restored by autologous stem-cell transplantation. Rheumatology 2003;42:375-9. https://doi.org/10.1093/rheumatology/keg074
  63. van Roon JAG, van Roy JLAM, Gmelig-Meyling FHJ, Lafeber FPJG, Bijlsma JWJ. Prevention and reversal of cartilage degradation in rheumatoid arthritis by interleukin-10 and interleukin-4. Arthritis Rheum 1996;39:829-35. https://doi.org/10.1002/art.1780390516
  64. Crawley E, Kay R, Sillibourne J, Patel P, Hutchinson I, Woo P. Polymorphic haplotypes of the interleukin-10 50 flanking region determine variable interleukin-10 transcription and are associated with particular phenotypes of juvenile rheumatoid arthritis. Arthritis Rheum 1999;42:1101-8. https://doi.org/10.1002/1529-0131(199906)42:6<1101::AID-ANR6>3.0.CO;2-Y
  65. van Roon JAG, van Roy JLAM, Duits A, Lafeber FPJG, Bijlsma JWJ. Proinflammatory cytokine production and cartilage damage due to rheumatoid synovial T helper-1 activation is inhibited by interleukin-4. Ann Rheum Dis 1995;54:836-40. https://doi.org/10.1136/ard.54.10.836
  66. Sugiyama E, Kuroda A, Taki H, Ikemoto M, Hori T, Yamashita N, et al. Interleukin 10 cooperates with interleukin 4 to suppress inflammatory cytokine production by freshly prepared adherent rheumatoid synovial cells. J Rheumatol 1995;22:2020-6.
  67. Fossiez F, Banchereau J, Murray R, van Kooten C, Garrone P, Lebecque S. Interleukin-17. Int Rev Immunol 1998;16:541-51. https://doi.org/10.3109/08830189809043008
  68. Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science 2003;299:1057-61. https://doi.org/10.1126/science.1079490
  69. Bennett CL, Christie J, Ramsdell F et al. The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat Genet 2001;27:20-1. https://doi.org/10.1038/83713
  70. de Kleer IM, Wedderburn LR, Taams LS, Patel A, Varsani H, Klein M, et al. CD4+CD25bright regulatory T cells actively regulate inflammation in the joints of patients with the remitting form of juvenile idiopathic arthritis. J Immunol 2004;172:6435-43. https://doi.org/10.4049/jimmunol.172.10.6435
  71. Ruprecht CR, Gattorno M, Ferlito F, Gregorio A, Martini A, Lanzavecchia A, et al. Coexpression of CD25 and CD27 identifies FoxP3+ regulatory T cells in inflamed synovia. J Exp Med 2005;201:1793-803. https://doi.org/10.1084/jem.20050085
  72. Korn T, Reddy J, Gao W, Bettelli E, Awasthi A, Petersen TR, et al. Myelin-specific regulatory T cells accumulate in the CNS but fail to control autoimmune inflammation. Nat Med 2007;13:423-31. https://doi.org/10.1038/nm1564
  73. Pasare C, Medzhitov R. Toll pathway-dependent blockade of CD4+ CD25+ T cell-mediated suppression by dendritic cells. Science 2003;299:1033-6. https://doi.org/10.1126/science.1078231
  74. Hahn YS, Kim JG. A clinical study on pauciarticular juvenile rheumatoid arthritis. Korean J Pediatr 1995;38:386-96.
  75. Hahn YS, Park JS, Kim JG. A clinical study on polyarticular juvenile arthritis: III. Polyarticular type. J Korean Rheum Assoc 1997;4:70-81.
  76. Siamopoulou-Mavridou A, Asimakopoulos D, Mavridis A, Skevas A, Moutsopoulos HM. Middle ear function in patients with juvenile chronic arthritis. Ann Rheum Dis 1990;49:620-3. https://doi.org/10.1136/ard.49.8.620
  77. Laiho K, Savolainen A, Kautiainen H, Kekki P, Kauppi M. The cervical spine in juvenile chronic arthritis. Spine J 2002;2:89-94.
  78. Barkin RE, Stillman JS, Potter TA. The spondylitis of juvenile rheumatoid arthritis. N Eng J Med 1955;253:1107-10. https://doi.org/10.1056/NEJM195512222532503
  79. Guillaume S, Prieur AM, Coste J, Job-Deslandre C. Long-term outcome and prognosis in oligoarticular-onset juvenile idiopathic arthritis. Arthritis Rheum 2000;43:1858-65. https://doi.org/10.1002/1529-0131(200008)43:8<1858::AID-ANR23>3.0.CO;2-A
  80. Ostrov BE. What is the significance of dry synovitis? Pediatr Rheumatol Online J 2004;2:114-8.
  81. Schaller JG. Juvenile rheumatoid arthritis. Pediatr Rev 1980;2:163-74. https://doi.org/10.1542/pir.2-6-163
  82. Kim JG, Jung JY, Yoon BY, Hahn YS. Clinical Observations on Juvenile Rheumatoid Arthritis: I. Systemic Type. J Korean Rheum Assoc 1994;1:175-82.
  83. Goldenberg J, Ferraz MB, Pessoa AP, Fonseca AS, Carvalho AC, Hilario MO, et al. Symptomatic cardiac involvement in juvenile rheumatoid arthritis. Int J Cardiol 1992;34:57-62. https://doi.org/10.1016/0167-5273(92)90082-E
  84. Bernstein MDB, Takahashi M, Hanson V. Cardiac involvement in juvenile rheumatoid arthritis. J Peditr 1974;85:313-7. https://doi.org/10.1016/S0022-3476(74)80107-1
  85. Toomey K, Hepburn B. Felty syndrome in juvenile arthritis. J Peditr 1985;106:254-5. https://doi.org/10.1016/S0022-3476(85)80299-7
  86. Schaller J, Beckwith B, Wedgwood RJ. Hepatic involvement in juvenile rheumatoid arthritis. J Peditr 1970;77:203-10. https://doi.org/10.1016/S0022-3476(70)80324-9
  87. Sawhney S, Woo P, Murray KJ. Macrophage activation syndrome: A potentially fatal complication of rheumatic disorders. Arch Dis Child 2001;85:421-6. https://doi.org/10.1136/adc.85.5.421
  88. Behrens EM, Beukelman T, Paessler M, Cron RQ. Occult macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis. J Rheumatol 2007;34:1133-8.
  89. Athreya BH. Is macrophage activation syndrome is a new entity? Clin Exp Rheumatol 2002;20:121-3.
  90. Ramanan AV, Schneider R. Macrophage activation syndrome following initiation of etanercept in a child with systemic onset juvenile rheumatoid arthritis. J Rheumatol 2003;30:401-3.
  91. Schneider R, Passo MH. Juvenile rheumatoid arthritis. Rheum Dis Clin North Am 2002;28:503-30. https://doi.org/10.1016/S0889-857X(02)00016-9
  92. Bowyer SL, Roettcher PA, Higgins GC, Adams B, Myers LK, Wallace C, et al. Health status of patients with juvenile rheumatoid arthritis at 1 and 5 years after diagnosis. J Rheumatol 2003;30:394-400.

Cited by

  1. Hemophagocytic lymphohistiocytosis: critical reappraisal of a potentially under-recognized condition vol.7, pp.4, 2010, https://doi.org/10.1007/s11684-013-0292-0
  2. The Role of Gender in Juvenile Idiopathic Arthritis-Associated Uveitis vol.2014, pp.None, 2014, https://doi.org/10.1155/2014/461078
  3. Do patients with juvenile idiopathic arthritis in remission exhibit active synovitis on joint ultrasound? vol.34, pp.7, 2014, https://doi.org/10.1007/s00296-013-2909-7
  4. Anti-inflammatory Activities of GyejigaChulBuTang on Lipopolysaccharide-stimulated RAW264.7 Cells vol.28, pp.3, 2014, https://doi.org/10.7778/jpkm.2014.28.3.047
  5. The Role of Sex in Uveitis and Ocular Inflammation vol.55, pp.3, 2015, https://doi.org/10.1097/iio.0000000000000072
  6. Patients with juvenile idiopathic arthritis in clinical remission with positive power Doppler signal in joint ultrasonography have an increased rate of clinical flare: a prospective study vol.15, pp.1, 2010, https://doi.org/10.1186/s12969-017-0208-7
  7. Investigational drugs for treatment of juvenile idiopathic arthritis vol.26, pp.4, 2010, https://doi.org/10.1080/13543784.2017.1301929
  8. Long-Term Effect of Pulsed Nd:YAG Laser in the Treatment of Children with Juvenile Rheumatoid Arthritis: A Randomized Controlled Trial vol.36, pp.8, 2010, https://doi.org/10.1089/pho.2018.4444
  9. Are We Right to Consider Mesenchymal Stem Cells to Be a New Perspective for Patients with Juvenile Idiopathic Arthritis? vol.66, pp.4, 2010, https://doi.org/10.1007/s00005-017-0493-3
  10. Low Vision Assessment: Complications from Juvenile Rhumethoid Arthritis vol.10, pp.2, 2010, https://doi.org/10.4236/ojoph.2020.102019
  11. Utilizing ultrasound findings of a single indicator joint to assess non-systemic juvenile idiopathic arthritis vol.19, pp.1, 2010, https://doi.org/10.1186/s12969-021-00550-0
  12. Best practices for recruitment of adolescents for biobanking and precision health research: a retrospective analysis comparing juvenile idiopathic arthritis cases with healthy controls vol.19, pp.1, 2010, https://doi.org/10.1186/s12969-021-00652-9
  13. Juvenile Idiopathic Arthritis: A Review of Novel Diagnostic and Monitoring Technologies vol.9, pp.12, 2021, https://doi.org/10.3390/healthcare9121683