, Volume 68, Issue 3, pp 319–337

Adult-Onset Still’s Disease

Pathogenesis, Clinical Manifestations and Therapeutic Advances
Review Article


Adult-onset Still’s disease (AOSD) is a rare, systemic inflammatory disease of unknown aetiology, characterized by daily high spiking fevers, evanescent rash and arthritis. Our objective was to review the most recent medical literature regarding advances in the understanding of disease pathogenesis, diagnosis and treatment. There is no single diagnostic test for AOSD, and diagnosis is based on clinical criteria and usually necessitates the exclusion of infectious, neoplastic and autoimmune diseases. Laboratory tests are nonspecific and reflect heightened immunological activity with leukocytosis, elevated acute phase reactants and, in particular, extremely elevated serum ferritin levels. Abnormal serum liver function tests are common, while rheumatoid factor and antinuclear antibodies are usually absent. Recent studies of the pathogenesis of the disease have suggested an important role for cytokines. Interleukin (IL)-1, IL-6 and IL-18, macrophage colony-stimulating factor, interferon-γ and tumour necrosis factor (TNF)-α are all elevated in patients with AOSD. Prognosis depends on the course of the disease and tends to be more favourable when systemic symptoms predominate.

Treatment includes the use of corticosteroids, often in combination with immunosuppressants (e.g. methotrexate, gold, azathioprine, leflunomide, tacrolimus, ciclosporin and cyclophosphamide) and intravenous immunoglobulin. Biological agents (e.g. anti-TNFα, anti-IL-1 and anti-IL-6) have been successfully used in refractory cases. Further progress has been hampered by the rarity and heterogeneity of the disease, which has not permitted the execution of randomized controlled studies.


  1. 1.
    Efthimiou P, Paik PK, Bielory L. Diagnosis and management of adult onset Still’s disease. Ann Rheum Dis 2006 May; 65(5): 564–72PubMedCrossRefGoogle Scholar
  2. 2.
    Bywaters EG. Still’s disease in the adult. Ann Rheum Dis 1971 Mar; 30(2): 121–33PubMedCrossRefGoogle Scholar
  3. 3.
    Magadur-Joly G, Billaud E, Barrier JH, et al. Epidemiology of adult Still’s disease: estimate of the incidence by a retrospective study in west France. Ann Rheum Dis 1995 Jul; 54(7): 587–90PubMedCrossRefGoogle Scholar
  4. 4.
    Ohta A, Yamaguchi M, Kaneoka H, et al. Adult Still’s disease: review of 228 cases from the literature. J Rheumatol 1987 Dec; 14(6): 1139–46PubMedGoogle Scholar
  5. 5.
    Wakai K, Ohta A, Tamakoshi A. Estimated prevalence and incidence of adult Still’s disease: findings by a nationwide epidemiological survey in Japan. J Epidemiol 1997; 7: 221–5PubMedCrossRefGoogle Scholar
  6. 6.
    Ohta A, Yamaguchi M, Tsunematsu T, et al. Adult Still’s disease: a multicenter survey of Japanese patients. J Rheumatol 1990 Aug; 17(8): 1058–63PubMedGoogle Scholar
  7. 7.
    Sampalis JS, Medsger Jr TA, Fries JF, et al. Risk factors for adult Still’s disease. J Rheumatol 1996 Dec; 23(12): 2049–54PubMedGoogle Scholar
  8. 8.
    Pouchot J, Sampalis JS, Beaudet F, et al. Adult Still’s disease: manifestations, disease course, and outcome in 62 patients. Medicine (Baltimore) 1991 Mar; 70(2): 118–36Google Scholar
  9. 9.
    Wouters JM, Reekers P, van de Putte LB. Adult-onset Still’s disease. Disease course and HLA associations. Arthritis Rheum 1986 Mar; 29(3): 415–8PubMedCrossRefGoogle Scholar
  10. 10.
    Miller ML, Aaron S, Jackson J, et al. HLA gene frequencies in children and adults with systemic onset juvenile rheumatoid arthritis. Arthritis Rheum 1985 Feb; 28(2): 146–50PubMedCrossRefGoogle Scholar
  11. 11.
    Joung CI, Lee HS, Lee SW, et al. Association between HLA-DR B1 and clinical features of adult onset Still’s disease in Korea. Clin Exp Rheumatol 2003 Jul–Aug; 21(4): 489–92PubMedGoogle Scholar
  12. 12.
    Fujii T, Nojima T, Yasuoka H, et al. Cytokine and immunogenetic profiles in Japanese patients with adult Still’s disease. Association with chronic articular disease. Rheumatology (Oxford) 2001 Dec; 40(12): 1398–404CrossRefGoogle Scholar
  13. 13.
    Chen DY, Lan JL, Hsieh TY, et al. Clinical manifestations, disease course, and complications of adult-onset Still’s disease in Taiwan. J Formos Med Assoc 2004 Nov; 103(11): 844–52PubMedGoogle Scholar
  14. 14.
    Masson C, Le Loet X, Liote F, et al. Adult Still’s disease: part I. Manifestations and complications in sixty-five cases in France. Rev Rhum Engl Ed 1995 Dec; 62(11): 748–57PubMedGoogle Scholar
  15. 15.
    Andres E, Kurtz JE, Perrin AE, et al. Retrospective monocentric study of 17 patients with adult Still’s disease, with special focus on liver abnormalities. Hepatogastroenterology 2003 Jan–Feb; 50(49): 192–5PubMedGoogle Scholar
  16. 16.
    van de Putte LB, Wouters JM. Adult-onset Still’s disease. Bailliere’s Clin Rheumatol 1991 Aug; 5(2): 263–75CrossRefGoogle Scholar
  17. 17.
    Pay S, Turkcapar N, Kalyoncu M, et al. A multicenter study of patients with adult-onset Still’s disease compared with systemic juvenile idiopathic arthritis. Clin Rheumatol 2006 Sep; 25(5): 639–44PubMedCrossRefGoogle Scholar
  18. 18.
    Mert A, Ozaras R, Tabak F, et al. Fever of unknown origin: a review of 20 patients with adult-onset Still’s disease. Clin Rheumatol 2003 May; 22(2): 89–93PubMedCrossRefGoogle Scholar
  19. 19.
    Bambery P, Thomas RJ, Malhotra HS, et al. Adult onset Still’s disease: clinical experience with 18 patients over 15 years in northern India. Ann Rheum Dis 1992 Apr; 51(4): 529–32PubMedCrossRefGoogle Scholar
  20. 20.
    Singh S, Samant R, Joshi VR. Adult onset Still’s disease: a study of 14 cases. Clin Rheumatol 2008 Jan; 27(1): 35–9PubMedCrossRefGoogle Scholar
  21. 21.
    Akritidis N, Sakkas LI. Adult onset Still’s disease. 16 cases. Presse Med 1995 Sep 16; 24(26): 1207–8Google Scholar
  22. 22.
    Evensen KJ, Nossent HC. Epidemiology and outcome of adult-onset Still’s disease in northern Norway. Scand J Rheumatol 2006 Jan–Feb; 35(1): 48–51PubMedCrossRefGoogle Scholar
  23. 23.
    Pouchot J, Ouakil H, Debin ML, et al. Adult Still’s disease associated with acute human parvovirus B19 infection. Lancet 1993 May 15; 341(8855): 1280–1PubMedCrossRefGoogle Scholar
  24. 24.
    Longo G, Luppi M, Bertesi M, et al. Still’s disease, severe thrombocytopenia, and acute hepatitis associated with acute parvovirus B19 infection. Clin Infect Dis 1998 Apr; 26(4): 994–5PubMedCrossRefGoogle Scholar
  25. 25.
    Wouters JM, van der Veen J, van de Putte LB, et al. Adult onset Still’s disease and viral infections. Ann Rheum Dis 1988 Sep; 47(9): 764–7PubMedCrossRefGoogle Scholar
  26. 26.
    Kadar J, Petrovicz E. Adult-onset Still’s disease. Best Pract Res Clin Rheumatol 2004 Oct; 18(5): 663–76PubMedCrossRefGoogle Scholar
  27. 27.
    Perez C, Artola V. Adult Still’s disease associated with Mycoplasma pneumoniae infection. Clin Infect Dis 2001 Mar 15; 32(6): E105–6PubMedCrossRefGoogle Scholar
  28. 28.
    Saviola G, Abdi Ali L, Shams Eddin S, et al. Clarithromycin in adult-onset Still’s disease: case report with a 1-year follow-up. Clin Exp Rheumatol 2004 May–Jun; 22(3): 379PubMedGoogle Scholar
  29. 29.
    Chen DY, Lan JL, Lin FJ, et al. Predominance of Th1 cytokine in peripheral blood and pathological tissues of patients with active untreated adult onset Still’s disease. Ann Rheum Dis 2004 Oct; 63(10): 1300–6PubMedCrossRefGoogle Scholar
  30. 30.
    Chen DY, Lan JL, Lin FJ, et al. Proinflammatory cytokine profiles in sera and pathological tissues of patients with active untreated adult onset Still’s disease. J Rheumatol 2004 Nov; 31(11): 2189–98PubMedGoogle Scholar
  31. 31.
    Hoshino T, Ohta A, Yang D, et al. Elevated serum interleukin 6, interferon-gamma, and tumor necrosis factor-alpha levels in patients with adult Still’s disease. J Rheumatol 1998 Feb; 25(2): 396–8PubMedGoogle Scholar
  32. 32.
    Sugiura T, Kawaguchi Y, Harigai M, et al. Association between adult-onset Still’s disease and interleukin-18 gene polymorphisms. Genes Immun 2002 Nov; 3(7): 394–9PubMedCrossRefGoogle Scholar
  33. 33.
    Ogata A, Kitano M, Yamanaka J, et al. Interleukin 18 and hepatocyte growth factor in fulminant hepatic failure of adult onset Still’s disease. J Rheumatol 2003 May; 30(5): 1093–6PubMedGoogle Scholar
  34. 34.
    Chen DY, Lan JL, Lin FJ, et al. Association of intercellular adhesion molecule-1 with clinical manifestations and interleukin-18 in patients with active, untreated adult-onset Still’s disease. Arthritis Rheum 2005 Jun 15; 53(3): 320–7PubMedCrossRefGoogle Scholar
  35. 35.
    Yamaguchi M, Ohta A, Tsunematsu T, et al. Preliminary criteria for classification of adult Still’s disease. J Rheumatol 1992 Mar; 19(3): 424–30PubMedGoogle Scholar
  36. 36.
    Cush JJ, Medsger Jr TA, Christy WC, et al. Adult-onset Still’s disease: clinical course and outcome. Arthritis Rheum 1987 Feb; 30(2): 186–94PubMedCrossRefGoogle Scholar
  37. 37.
    Fautrel B, Zing E, Golmard JL, et al. Proposal for a new set of classification criteria for adult-onset Still disease. Medicine (Baltimore) 2002 May; 81(3): 194–200CrossRefGoogle Scholar
  38. 38.
    Zhiyong Z, Bingjun L, Xiaoju L, et al. Fever of unknown origin: a report from China of 208 cases. Int J Clin Pract 2003 Sep; 57(7): 592–6PubMedGoogle Scholar
  39. 39.
    Wouters JM, van de Putte LB. Adult-onset Still’s disease; clinical and laboratory features, treatment and progress of 45 cases. Q J Med 1986 Nov; 61(235): 1055–65PubMedGoogle Scholar
  40. 40.
    Larson EB. Adult Still’s disease: recognition of a clinical syndrome and recent experience. West J Med 1985 May; 142(5): 665–71PubMedGoogle Scholar
  41. 41.
    Cush JJ. Adult-onset Still’s disease. Bull Rheum Dis 2000; 49(6): 1–4PubMedGoogle Scholar
  42. 42.
    Medsger Jr TA, Christy WC. Carpal arthritis with ankylosis in late onset Still’s disease. Arthritis Rheum 1976 Mar–Apr; 19(2): 232–42PubMedCrossRefGoogle Scholar
  43. 43.
    Bjorkengren AG, Pathria MN, Sartoris DJ, et al. Carpal alterations in adult-onset Still disease, juvenile chronic arthritis, and adult-onset rheumatoid arthritis: comparative study. Radiology 1987 Nov; 165(2): 545–8PubMedGoogle Scholar
  44. 44.
    Cabane J, Michon A, Ziza JM, et al. Comparison of long term evolution of adult onset and juvenile onset Still’s disease, both followed up for more than 10 years. Ann Rheum Dis 1990 May; 49(5): 283–5PubMedCrossRefGoogle Scholar
  45. 45.
    Dino O, Provenzano G, Giannuoli G, et al. Fulminant hepatic failure in adult onset Still’s disease. J Rheumatol 1996; 23: 784–5PubMedGoogle Scholar
  46. 46.
    McFarlane M, Harth M, Wall WJ. Liver transplant in adult Still’s disease. J Rheumatol 1997 Oct; 24(10): 2038–41PubMedGoogle Scholar
  47. 47.
    Hirohata S, Kamoshita H, Taketani T, et al. Adult Still’s disease complicated with adult respiratory distress. Arch Intern Med 1986 Dec; 146(12): 2409–10PubMedCrossRefGoogle Scholar
  48. 48.
    Stoica GS, Cohen RI, Rossoff LJ. Adult Still’s disease and respiratory failure in a 74 year old woman. Postgrad Med J 2002 Feb; 78(916): 97–8PubMedCrossRefGoogle Scholar
  49. 49.
    Suleiman M, Wolfovitz E, Boulman N, et al. Adult onset Still’s disease as a cause of ARDS and acute respiratory failure. Scand J Rheumatol 2002; 31(3): 181–3PubMedGoogle Scholar
  50. 50.
    Sachs RN, Talvard O, Lanfranchi J. Myocarditis in adult Still’s disease. Int J Cardiol 1990 Jun; 27(3): 377–80PubMedCrossRefGoogle Scholar
  51. 51.
    Bennett AN, Peterson P, Sangle S, et al. Adult onset Still’s disease and collapsing glomerulopathy: successful treatment with intravenous immunoglobulins and mycophenolate mofetil. Rheumatology (Oxford) 2004 Jun; 43(6): 795–9CrossRefGoogle Scholar
  52. 52.
    Kumar S, Sheaff M, Yaqoob M. Collapsing glomerulopathy in adult still’s disease. Am J Kidney Dis 2004 May; 43(5): e4–10PubMedCrossRefGoogle Scholar
  53. 53.
    Wendling D, Hory B, Blanc D. Adult Still’s disease and mesangial glomerulonephritis: report of two cases. Clin Rheumatol 1990; 9: 95–9PubMedCrossRefGoogle Scholar
  54. 54.
    Wendling D, Humbert PG, Billerey C, et al. Adult onset Still’s disease and related renal amyloidosis. Ann Rheum Dis 1991 Apr; 50(4): 257–9PubMedCrossRefGoogle Scholar
  55. 55.
    Arlet JB, Le TH, Marinho A, et al. Reactive haemophagocytic syndrome in adult onset Still’s disease: report of 6 patients and review of the literature. Ann Rheum Dis 2006 Dec; 65(12): 1596–601PubMedCrossRefGoogle Scholar
  56. 56.
    Denault A, Dimopoulos MA, Fitzcharles MA. Meningoencephalitis and peripheral neuropathy complicating adult Still’s disease. J Rheumatol 1990 May; 17(5): 698–700PubMedGoogle Scholar
  57. 57.
    Markusse HM, Stolk B, van der Mey AG, et al. Sensorineural hearing loss in adult onset Still’s disease. Ann Rheum Dis 1988 Jul; 47(7): 600–2PubMedCrossRefGoogle Scholar
  58. 58.
    Fautrel B, Le Moel G, Saint-Marcoux B, et al. Diagnostic value of ferritin and glycosylated ferritin in adult onset Still’s disease. J Rheumatol 2001 Feb; 28(2): 322–9PubMedGoogle Scholar
  59. 59.
    Fautrel B. Ferritin levels in adult Still’s disease: any sugar? Joint Bone Spine 2002 Jun; 69(4): 355–7PubMedCrossRefGoogle Scholar
  60. 60.
    Van Reeth C, Le Moel G, Lasne Y, et al. Serum ferritin and isoferritins are tools for diagnosis of active adult Still’s disease. J Rheumatol 1994 May; 21(5): 890–5PubMedGoogle Scholar
  61. 61.
    Akritidis N, Giannakakis Y, Sakkas L. Very high serum ferritin levels in adult-onset Still’s disease. Br J Rheumatol 1997 May; 36(5): 608–9PubMedCrossRefGoogle Scholar
  62. 62.
    Akritidis N, Giannakakis I, Giouglis T. Ferritin levels and response to treatment in patients with adult Still’s disease. J Rheumatol 1996 Jan; 23(1): 201–2PubMedGoogle Scholar
  63. 63.
    Kirino Y, Takeno M, Iwasaki M, et al. Increased serum HO-1 in hemophagocytic syndrome and adult-onset Still’s disease: use in the differential diagnosis of hyperferritinemia. Arthritis Res Ther 2005; 7(3): R616–24PubMedCrossRefGoogle Scholar
  64. 64.
    Min JK, Cho CS, Kim HY, et al. Bone marrow findings in patients with adult Still’s disease. Scand J Rheumatol 2003; 32(2): 119–21PubMedCrossRefGoogle Scholar
  65. 65.
    Fujii T, Suwa A, Mimori T, et al. Chronic arthritis and carpo:metacarpal ratio in Japanese patients with adult Still’s disease. J Rheumatol 1998 Dec; 25(12): 2402–7PubMedGoogle Scholar
  66. 66.
    Vane JR. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nature New Biol 1971 Jun 23; 231(25): 232–5PubMedGoogle Scholar
  67. 67.
    Masson C, Le Loet X, Liote F, et al. Adult Still’s disease: part II. Management, outcome, and prognostic factors. Rev Rhum Engl Ed 1995 Dec; 62(11): 758–65PubMedGoogle Scholar
  68. 68.
    Li YH, Brauner A, Jonsson B, et al. Inhibition of macrophage proinflammatory cytokine expression by steroids and recombinant IL-10. Biol Neonate 2001 Aug; 80(2): 124–32PubMedCrossRefGoogle Scholar
  69. 69.
    Hu X, Li WP, Meng C, et al. Inhibition of IFN-gamma signaling by glucocorticoids. J Immunol 2003 May 1; 170(9): 4833–9PubMedGoogle Scholar
  70. 70.
    Migita K, Eguchi K, Kawabe Y, et al. Apoptosis induction in human peripheral blood T lymphocytes by high-dose steroid therapy. Transplantation 1997 Feb 27; 63(4): 583–7PubMedCrossRefGoogle Scholar
  71. 71.
    De A, Blotta HM, Mamoni RL, et al. Effects of dexamethasone on lymphocyte proliferation and cytokine production in rheumatoid arthritis. J Rheumatol 2002 Jan; 29(1): 46–51PubMedGoogle Scholar
  72. 72.
    Nakano T, Ohara O, Teraoka H, et al. Glucocorticoids suppress group II phospholipase A2 production by blocking mRNA synthesis and post-transcriptional expression. J Biol Chem 1990 Jul 25; 265(21): 12745–8PubMedGoogle Scholar
  73. 73.
    Khraishi M, Fam AG. Treatment of fulminant adult Still’s disease with intravenous pulse methylprednisolone therapy. J Rheumatol 1991 Jul; 18(7): 1088–90PubMedGoogle Scholar
  74. 74.
    Koizumi R, Tsukada Y, Ideura H, et al. Treatment of adult Still’s disease with dexamethasone, an alternative to prednisolone. Scand J Rheumatol 2000; 29(6): 396–8PubMedCrossRefGoogle Scholar
  75. 75.
    Da Silva JA, Jacobs JW, Kirwan JR, et al. Safety of low dose glucocorticoid treatment in rheumatoid arthritis: published evidence and prospective trial data. Ann Rheum Dis 2006 Mar; 65(3): 285–93PubMedCrossRefGoogle Scholar
  76. 76.
    Shojania K, Chalmers A, Rangno K. Cyclosporin A in the treatment of adult Still’s disease. J Rheumatol 1995 Jul; 22(7): 1391–2PubMedGoogle Scholar
  77. 77.
    Cefle A. Leflunomide and azathioprine combination in refractory adult-onset Still’s disease. Ann Pharmacother 2005 Apr; 39(4): 764–7PubMedCrossRefGoogle Scholar
  78. 78.
    Elkon KB, Hughes GR, Bywaters EG, et al. Adult-onset Still’s disease: twenty-year followup and further studies of patients with active disease. Arthritis Rheum 1982 Jun; 25(6): 647–54PubMedCrossRefGoogle Scholar
  79. 79.
    Murakami K, Fujii T, Yukawa N, et al. Successful treatment of a patient with refractory adult Still’s disease by tacrolimus. Modern Rheumatology / the Japan Rheumatism Association 2007; 17(2): 167–70PubMedGoogle Scholar
  80. 80.
    Chan ES, Cronstein BN. Molecular action of methotrexate in inflammatory diseases. Arthritis Res 2002; 4(4): 266–73PubMedCrossRefGoogle Scholar
  81. 81.
    Cronstein BN, Naime D, Ostad E. The antiinflammatory effects of methotrexate are mediated by adenosine. Adv Expe Med Biol 1994; 370: 411–6Google Scholar
  82. 82.
    Cronstein BN, Eberle MA, Gruber HE, et al. Methotrexate inhibits neutrophil function by stimulating adenosine release from connective tissue cells. Proc Natl Acad Sci U S A 1991 Mar 15; 88(6): 2441–5PubMedCrossRefGoogle Scholar
  83. 83.
    Fautrel B, Borget C, Rozenberg S, et al. Corticosteroid sparing effect of low dose methotrexate treatment in adult Still’s disease. J Rheumatol 1999 Feb; 26(2): 373–8PubMedGoogle Scholar
  84. 84.
    Fujii T, Akizuki M, Kameda H, et al. Methotrexate treatment in patients with adult onset Still’s disease: retrospective study of 13 Japanese cases. Ann Rheum Dis 1997 Feb; 56(2): 144–8PubMedCrossRefGoogle Scholar
  85. 85.
    Aydintug AO, D’Cruz D, Cervera R, et al. Low dose methotrexate treatment in adult Still’s disease. J Rheumatol 1992 Mar; 19(3): 431–5PubMedGoogle Scholar
  86. 86.
    Asherson RA, Pascoe L. Adult onset Still’s disease: response to Enbrel. Ann Rheum Dis 2002 Sep; 61(9): 859–60; author reply 60PubMedCrossRefGoogle Scholar
  87. 87.
    Husni ME, Maier AL, Mease PJ, et al. Etanercept in the treatment of adult patients with Still’s disease. Arthritis Rheum 2002 May; 46(5): 1171–6PubMedCrossRefGoogle Scholar
  88. 88.
    Cavagna L, Caporali R, Epis O, et al. Infliximab in the treatment of adult Still’s disease refractory to conventional therapy. Clin Exp Rheumatol 2001 May–Jun; 19(3): 329–32PubMedGoogle Scholar
  89. 89.
    Kokkinos A, Iliopoulos A, Greka P, et al. Successful treatment of refractory adult-onset Still’s disease with infliximab: a prospective, non-comparative series of four patients. Clin Rheumatol 2004 Feb; 23(1): 45–9PubMedCrossRefGoogle Scholar
  90. 90.
    Huffstutter J, Sienknecht C. Treatment of resistant adult Still’s disease with infliximab: a report of 2 cases. J Clin Rheumatol 2004; 10(4): 218–21PubMedCrossRefGoogle Scholar
  91. 91.
    Bonilla Hernan MG, Cobo Ibanez T, de Miguel Mendieta E, et al. Infliximab (anti-TNF-alpha) treatment in patients with adult Still’s disease: experience in 2 cases [in Spanish]. An Med Interna 2004 Jan; 21(1): 23–6PubMedGoogle Scholar
  92. 92.
    Caramaschi P, Biasi D, Carletto A, et al. A case of adult onset Still’s disease treated with infliximab [letter]. Clin Exp Rheumatol 2002 Jan–Feb; 20(1): 113PubMedGoogle Scholar
  93. 93.
    Dilhuydy MS, Vatan R, Etienne G, et al. Prolonged efficacy of infliximab for refractory adult-onset Still’s disease. Clin Exp Rheumatol 2005 Jan–Feb; 23(1): 121–2PubMedGoogle Scholar
  94. 94.
    Fautrel B, Sibilia J, Mariette X, et al. Tumour necrosis factor alpha blocking agents in refractory adult Still’s disease: an observational study of 20 cases. Ann Rheum Dis 2005 Feb; 64(2): 262–6PubMedCrossRefGoogle Scholar
  95. 95.
    Benucci M, Li GF, Del Rosso A, et al. Adalimumab (anti-TNF-alpha) therapy to improve the clinical course of adult-onset Still’s disease: the first case report [letter]. Clin Exp Rheumatol 2005 Sep–Oct; 23(5): 733PubMedGoogle Scholar
  96. 96.
    Iwamoto M, Nara H, Hirata D, et al. Humanized monoclonal anti-interleukin-6 receptor antibody for treatment of intractable adult-onset Still’s disease. Arthritis Rheum 2002 Dec; 46(12): 3388–9PubMedCrossRefGoogle Scholar
  97. 97.
    Godinho F, Santos MJ, Canas Da Silva J. Refractory adult onset Still’s disease successfully treated with anakinra. Ann Rheum Dis 2005; 64: 647–8CrossRefGoogle Scholar
  98. 98.
    Aelion J, Odhav S. Prompt response to treatment with anakinra in adult onset Still’s disease. Ann Rheum Dis 2004; 63 Suppl.: 281Google Scholar
  99. 99.
    Fitzgerald AA, Leclercq SA, Yan A, et al. Rapid responses to anakinra in patients with refractory adult-onset Still’s disease. Arthritis Rheum 2005 Jun; 52(6): 1794–803PubMedCrossRefGoogle Scholar
  100. 100.
    Ortiz Z, Shea B, Suarez Almazor M, et al. Folic acid and folinic acid for reducing side effects in patients receiving methotrexate for rheumatoid arthritis. Cochrane Database Syst Rev 2000; (2): CD000951PubMedGoogle Scholar
  101. 101.
    Joyce DA, Will RK, Hoffman DM, et al. Exacerbation of rheumatoid arthritis in patients treated with methotrexate after administration of folinic acid. Ann Rheum Dis 1991 Dec; 50(12): 913–4PubMedCrossRefGoogle Scholar
  102. 102.
    Endresen GK, Husby G. Folate supplementation during methotrexate treatment of patients with rheumatoid arthritis: an update and proposals for guidelines. Scand J Rheumatol 2001; 30(3): 129–34PubMedCrossRefGoogle Scholar
  103. 103.
    Sathi N, Dawson J. Methotrexate-induced pancytopenia associated with co-prescription of penicillin and trimethoprim. Clin Rheumatol 2007 Jan; 26(1): 134–5PubMedCrossRefGoogle Scholar
  104. 104.
    Michel M, Hayem G, Rat AC, et al. Fatal infectious complications in 2 patients with adult onset Still disease [in French]. Rev Med Interne 1996; 17(5): 407–9PubMedCrossRefGoogle Scholar
  105. 105.
    Janssen HL, van Laar JM, van Hoek B, et al. Severe hepatitis and pure red cell aplasia in adult Still’s disease: good response to immunosuppressive therapy. Dig Dis Sci 1999 Aug; 44(8): 1639–42PubMedCrossRefGoogle Scholar
  106. 106.
    Ott SJ, Baron A, Berghaus T, et al. Liver failure in adult Still’s disease during corticosteroid treatment. Eur J Gastroenterol Hepatol 2003 Jan; 15(1): 87–90PubMedCrossRefGoogle Scholar
  107. 107.
    Weinblatt ME. Toxicity of low dose methotrexate in rheumatoid arthritis. J Rheumatol Suppl 1985 Dec; 12 Suppl. 12: 35–9PubMedGoogle Scholar
  108. 108.
    Preet Singh Y, Aggarwal A, Misra R, et al. Low-dose methotrexate-induced pancytopenia. Clin Rheumatol 2007 Jan; 26(1): 84–7PubMedCrossRefGoogle Scholar
  109. 109.
    Reginato AJ, Schumacher Jr HR, Baker DG, et al. Adult onset Still’s disease: experience in 23 patients and literature review with emphasis on organ failure. Semin Arthritis Rheum 1987 Aug; 17(1): 39–57PubMedCrossRefGoogle Scholar
  110. 110.
    Weinblatt ME, Trentham DE, Fraser PA, et al. Long-term prospective trial of low-dose methotrexate in rheumatoid arthritis. Arthritis Rheum 1988 Feb; 31(2): 167–75PubMedCrossRefGoogle Scholar
  111. 111.
    Hunstad DA, French AR. Histoplasmosis in a child with JRA on low-dose methotrexate. Rheumatology (Oxford) 2007 Jan; 46(1): 177–8CrossRefGoogle Scholar
  112. 112.
    Chim CS, Pang YY, Ooi GC, et al. EBV-associated synovial lymphoma in a chronically inflamed joint in rheumatoid arthritis receiving prolonged methotrexate treatment. Haematologica 2006 Aug; 91 (8 Suppl.): ECR31PubMedGoogle Scholar
  113. 113.
    Takeyama J, Sato A, Nakano K, et al. Epstein-Barr virus associated Hodgkin lymphoma in a 9-year-old girl receiving long-term methotrexate therapy for juvenile idiopathic arthritis. J Pediatr Hematol Oncol 2006 Sep; 28(9): 622–4PubMedCrossRefGoogle Scholar
  114. 114.
    Kazatchkine MD, Kaveri SV. Immunomodulation of autoimmune and inflammatory diseases with intravenous immune globulin. N Engl J Med 2001 Sep 6; 345(10): 747–55PubMedCrossRefGoogle Scholar
  115. 115.
    Singh S, Bansal A, Gupta A, et al. Kawasaki disease: a decade of experience from North India. Int Heart J 2005 Jul; 46(4): 679–89PubMedCrossRefGoogle Scholar
  116. 116.
    Silverman ED, Cawkwell GD, Lovell DJ, et al. Intravenous immunoglobulin in the treatment of systemic juvenile rheumatoid arthritis: a randomized placebo controlled trial. Pediatric Rheumatology Collaborative Study Group. J Rheumatol 1994 Dec; 21(12): 2353–8PubMedGoogle Scholar
  117. 117.
    Mahmud T, Hughes GR. Intravenous immunoglobulin in the treatment of refractory adult Still’s disease. J Rheumatol 1999 Sep; 26(9): 2067–8PubMedGoogle Scholar
  118. 118.
    Vignes S, Wechsler B, Amoura Z, et al. Intravenous immunoglobulin in adult Still’s disease refractory to non-steroidal anti-inflammatory drugs. Clin Exp Rheumatol 1998 May–Jun; 16(3): 295–8PubMedGoogle Scholar
  119. 119.
    Permal S, Wechsler B, Cabane J, et al. Treatment of Still disease in adults with intravenous immunoglobulins. Rev Med Interne 1995; 16: 250–4PubMedCrossRefGoogle Scholar
  120. 120.
    Kuek A, Weerakoon A, Ahmed K, et al. Adult-onset Still’s disease and myocarditis: successful treatment with intravenous immunoglobulin and maintenance of remission with etanercept. Rheumatology (Oxford) 2007 Jun; 46(6): 1043–4CrossRefGoogle Scholar
  121. 121.
    Katz U, Achiron A, Sherer Y, et al. Safety of intravenous immunoglobulin (IVIG) therapy. Autoimmun Rev 2007 Mar; 6(4): 257–9PubMedCrossRefGoogle Scholar
  122. 122.
    Ryan ME, Webster ML, Statler JD. Adverse effects of intravenous immunoglobulin therapy. Clin Pediatrics 1996 Jan; 35(1): 23–31CrossRefGoogle Scholar
  123. 123.
    Hamrock DJ. Adverse events associated with intravenous immunoglobulin therapy. Int Immunopharmacol 2006 Apr; 6(4): 535–42PubMedCrossRefGoogle Scholar
  124. 124.
    Burks AW, Sampson HA, Buckley RH. Anaphylactic reactions after gammaglobulin administration in patients with hypogam-maglobulinemia: detection of IgE antibodies to IgA. N Engl J Med 1986; 314: 550–4CrossRefGoogle Scholar
  125. 125.
    Oh YB, Bae SC, Jung JH, et al. Secondary renal amyloidosis in adult onset Still’s disease: case report and review of the literature. Korean J Intern Med 2000 Jul; 15(2): 131–4PubMedGoogle Scholar
  126. 126.
    Kraetsch HG, Antoni C, Kalden JR, et al. Successful treatment of a small cohort of patients with adult onset of Still’s disease with infliximab: first experiences. Ann Rheum Dis 2001 Nov; 60 Suppl. 3: iii55–7PubMedGoogle Scholar
  127. 127.
    Dechant C, Schauenberg P, Antoni CE, et al. Long-term outcome of TNF blockade in adult-onset Still’s disease [in German]. Dtsch Med Wochenschr 2004 Jun 4; 129(23): 1308–12PubMedCrossRefGoogle Scholar
  128. 128.
    Michel M, Duvoux C, Hezode C, et al. Fulminant hepatitis after infliximab in a patient with hepatitis B virus treated for an adult onset still’s disease. J Rheumatol 2003 Jul; 30(7): 1624–5PubMedGoogle Scholar
  129. 129.
    Olivieri I, de Stefano G, Padula A, et al. Infliximab in a case of early adult-onset Still’s disease. Clin Rheumatol 2003 Oct; 22(4-5): 369–70PubMedCrossRefGoogle Scholar
  130. 130.
    Serratrice J, Granel B, Disdier P, et al. Resolution with etaner-cept of nephrotic syndrome due to renal AA amyloidosis in adult Still’s disease. Am J Med 2003 Nov; 115(7): 589–90PubMedCrossRefGoogle Scholar
  131. 131.
    Kumari R, Uppal SS. Prolonged remission in adult-onset Still’s disease with etanercept. Clin Rheumatol 2006 Feb; 25(1): 106–8PubMedCrossRefGoogle Scholar
  132. 132.
    Asherson RA, Pascoe L. Adult onset Still’s disease: response to Enbrel. Ann Rheum Dis 2002 Sep; 61(9): 859–60PubMedCrossRefGoogle Scholar
  133. 133.
    Haraoui B, Bourrelle D, Kaminska E. Anakinra in the treatment of adult onset Still’s disease. Ann Rheum Dis 2004 Jul 1; 63 Suppl.: 293–4Google Scholar
  134. 134.
    Kotter I, Wacker A, Koch S, et al. Anakinra in patients with treatment-resistant adult-onset Still’s disease: four case reports with serial cytokine measurements and a review of the literature. Semin Arthritis Rheum 2007 Dec; 37(3): 189–97PubMedCrossRefGoogle Scholar
  135. 135.
    Kalliolias GD, Georgiou PE, Antonopoulos IA, et al. Anakinra treatment in patients with adult-onset Still’s disease is fast, effective, safe and steroid sparing: experience from an uncontrolled trial. Ann Rheum Dis 2007 Jun; 66(6): 842–3PubMedCrossRefGoogle Scholar
  136. 136.
    Vasques Godinho FM, Parreira Santos MJ, Canas da Silva J. Refractory adult onset Still’s disease successfully treated with anakinra. Ann Rheum Dis 2005 Apr; 64(4): 647–8PubMedCrossRefGoogle Scholar
  137. 137.
    Rudinskaya A, Trock DH. Successful treatment of a patient with refractory adult-onset Still disease with anakinra. J Clin Rheumatol 2003 Oct; 9(5): 330–2PubMedCrossRefGoogle Scholar
  138. 138.
    Quartuccio L, De Vita S. Interleukin 1 receptor antagonist therapy-induced thrombocytopenia in adult onset Still’s disease. J Rheumatol 2007 Apr; 34(4): 892–3PubMedGoogle Scholar
  139. 139.
    Chu C, Hughes G, Karr N, et al. Interleukin-1 blockade is an effective treatment of adult onset Still’s disease. Arthritis Rheum 2005; 52(12): 4101Google Scholar
  140. 140.
    Mohler KM, Torrance DS, Smith CA, et al. Soluble tumor necrosis factor (TNF) receptors are effective therapeutic agents in lethal endotoxemia and function simultaneously as both TNF carriers and TNF antagonists. J Immunol 1993 Aug 1; 151(3): 1548–61PubMedGoogle Scholar
  141. 141.
    Efthimiou P, Markenson JA. Role of biological agents in immune-mediated inflammatory diseases. South Med J 2005 Feb; 98(2): 192–204PubMedCrossRefGoogle Scholar
  142. 142.
    Agnholt J, Dahlerup JF, Kaltoft K. The effect of etanercept and infliximab on the production of tumour necrosis factor alpha, interferon-gamma and GM-CSF in in vivo activated intestinal T lymphocyte cultures. Cytokine 2003 Aug 7; 23(3): 76–8PubMedCrossRefGoogle Scholar
  143. 143.
    Fleischmann R, Iqbal I, Nandeshwar P, et al. Safety and efficacy of disease-modifying anti-rheumatic agents: focus on the benefits and risks of etanercept. Drug Saf 2002; 25(3): 173–97PubMedCrossRefGoogle Scholar
  144. 144.
    Lovell DJ, Reiff A, Jones OY, et al. Long-term safety and efficacy of etanercept in children with polyarticular-course juvenile rheumatoid arthritis. Arthritis Rheum 2006 Jun; 54(6): 1987–94PubMedCrossRefGoogle Scholar
  145. 145.
    La Montagna G, Valentini G. Listeria monocytogenes meningitis in a patient receiving etanercept for Still’s disease [letter]. Clin Exp Rheumatol 2005 Jan–Feb; 23(1): 121PubMedGoogle Scholar
  146. 146.
    Khanna D, McMahon M, Furst DE. Safety of tumour necrosis factor-alpha antagonists. Drug Saf 2004; 27(5): 307–24PubMedCrossRefGoogle Scholar
  147. 147.
    Nurmohamed MT, Dijkmans BA. Efficacy, tolerability and cost effectiveness of disease-modifying antirheumatic drugs and biologic agents in rheumatoid arthritis. Drugs 2005; 65(5): 661–94PubMedCrossRefGoogle Scholar
  148. 148.
    Kuek A, Hazleman BL, Ostor AJ. Immune-mediated inflammatory diseases (IMIDs) and biologic therapy: a medical revolution. Postgrad Med J 2007 Apr; 83(978): 251–60PubMedCrossRefGoogle Scholar
  149. 149.
    Efthimiou P, Georgy S. Pathogenesis and management of adult-onset Still’s disease. Semin Arthritis Rheum 2006 Dec; 36(3): 144–52PubMedCrossRefGoogle Scholar
  150. 150.
    Arend WP, Welgus HG, Thompson RC, et al. Biological properties of recombinant human monocyte-derived interleukin 1 receptor antagonist. J Clin Invest 1990 May; 85(5): 1694–7PubMedCrossRefGoogle Scholar
  151. 151.
    den Breeder AA, de Jong E, Franssen MJ, et al. Observational study on efficacy, safety, and drug survival of anakinra in rheumatoid arthritis patients in clinical practice. Ann Rheum Dis 2006 Jun; 65(6): 760–2CrossRefGoogle Scholar
  152. 152.
    Fleischmann RM, Tesser J, Schiff MH, et al. Safety of extended treatment with anakinra in patients with rheumatoid arthritis. Ann Rheum Dis 2006 Aug; 65(8): 1006–12PubMedCrossRefGoogle Scholar
  153. 153.
    Ruiz PJ, Masliah E, Doherty TA, et al. Cardiac death in a patient with adult-onset Still’s disease treated with the interleukin 1 receptor inhibitor anakinra. Ann Rheum Dis 2007 Mar; 66(3): 422–3PubMedCrossRefGoogle Scholar
  154. 154.
    Yokota S, Miyamae T, Imagawa T, et al. Therapeutic efficacy of humanized recombinant anti-interleukin-6 receptor antibody in children with systemic-onset juvenile idiopathic arthritis. Arthritis Rheum 2005 Mar; 52(3): 818–25PubMedCrossRefGoogle Scholar
  155. 155.
    Woo P, Wilkinson N, Prieur AM, et al. Open label phase II trial of single, ascending doses of MRA in Caucasian children with severe systemic juvenile idiopathic arthritis: proof of principle of the efficacy of IL-6 receptor blockade in this type of arthritis and demonstration of prolonged clinical improvement. Arthritis Res Ther 2005; 7 (6): R1281–8CrossRefGoogle Scholar
  156. 156.
    Nishimoto N, Kishimoto T. Inhibition of IL-6 for the treatment of inflammatory diseases. Curr Opin Pharmacol 2004 Aug; 4(4): 386–91PubMedCrossRefGoogle Scholar
  157. 157.
    Maini RN, Taylor PC, Szechinski J, et al. Double-blind randomized controlled clinical trial of the interleukin-6 receptor antagonist, tocilizumab, in European patients with rheumatoid arthritis who had an incomplete response to methotrexate. Arthritis Rheum 2006 Sep; 54(9): 2817–29PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2008

Authors and Affiliations

  1. 1.Department of MedicineLincoln Medical and Mental Health CenterNew YorkUSA
  2. 2.Rheumatology DivisionLincoln Medical and Mental Health CenterNew YorkUSA
  3. 3.Weill Cornell Medical CollegeNew YorkUSA

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