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Clinical manifestations and diagnosis of adult Still's disease

Lisa A Mandl, MD, MPH
Section Editor
James R O'Dell, MD
Deputy Editor
Paul L Romain, MD


Adult Still’s disease (ASD) is an inflammatory disorder characterized by quotidian (daily) fevers, arthritis, and an evanescent rash. First described in children by George Still in 1896, “Still’s disease” has become the eponymous term for systemic juvenile idiopathic arthritis [1]. In 1971, the term “adult Still’s disease” was used to describe a series of adult patients who had features similar to the children with systemic juvenile idiopathic arthritis and did not fulfill criteria for classic rheumatoid arthritis (RA) [2]. (See "Systemic juvenile idiopathic arthritis: Clinical manifestations and diagnosis".)

The clinical manifestations and diagnosis of ASD will be reviewed here. The treatment and prognosis of ASD are presented separately. (See "Treatment of adult Still's disease".)


The etiology of adult Still’s disease (ASD) is unknown; both genetic factors and a variety of infectious triggers have been suggested as important, but there has been no proof of an infectious etiology, and the evidence supporting a role for genetic factors has been mixed. It is uncertain whether all patients with ASD share the same etiopathogenic factors.

Proposed pathogens have included numerous viruses [3-7]; suspected bacterial pathogens include Yersinia enterocolitica and Mycoplasma pneumoniae [5,8].

As an example of studies of the immunogenetics of ASD, in a series of 62 French patients, human leukocyte antigen (HLA)-B17, -B18, -B35, and -DR2 were associated with ASD [9]. However, other studies have not confirmed these findings [10]. Familial cases are uncommon, and there have been few reports of cases in twins [11].


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Literature review current through: Sep 2016. | This topic last updated: Jan 2, 2016.
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  1. Still GF. On a Form of Chronic Joint Disease in Children. Med Chir Trans 1897; 80:47.
  2. Bywaters EG. Still's disease in the adult. Ann Rheum Dis 1971; 30:121.
  3. Huang SH, DeCoteau WE. Adult-onset Still's disease: an unusual presentation of rubella infection. Can Med Assoc J 1980; 122:1275.
  4. Wouters JM, van der Veen J, van de Putte LB, de Rooij DJ. Adult onset Still's disease and viral infections. Ann Rheum Dis 1988; 47:764.
  5. Ohta A, Yamaguchi M, Tsunematsu T, et al. Adult Still's disease: a multicenter survey of Japanese patients. J Rheumatol 1990; 17:1058.
  6. Pouchot J, Ouakil H, Debin ML, Vinceneux P. Adult Still's disease associated with acute human parvovirus B19 infection. Lancet 1993; 341:1280.
  7. Efthimiou P, Paik PK, Bielory L. Diagnosis and management of adult onset Still's disease. Ann Rheum Dis 2006; 65:564.
  8. Colebunders R, Stevens WJ, Vanagt E, Snoeck J. Adult Still's disease caused by Yersinia enterocolitica infection. Arch Intern Med 1984; 144:1880.
  9. Pouchot J, Sampalis JS, Beaudet F, et al. Adult Still's disease: manifestations, disease course, and outcome in 62 patients. Medicine (Baltimore) 1991; 70:118.
  10. Sampalis JS, Medsger TA Jr, Fries JF, et al. Risk factors for adult Still's disease. J Rheumatol 1996; 23:2049.
  11. Kahn MF. Adult Still's disease. Still many issues unresolved. J Rheumatol 1996; 23:2015.
  12. 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; 54:587.
  13. Uson J, Peña JM, del Arco A, et al. Still's disease in a 72-year-old man. J Rheumatol 1993; 20:1608.
  14. Steffe LA, Cooke CL. Still's disease in a 70-year-old woman. JAMA 1983; 249:2062.
  15. Pouchot, J, Sampalis, JS, Beaudet, F, et al. Adult onset Still's disease: Manifestations, disease course and outcome in 62 patients. Medicine (Baltimore) 1991; 70:118.
  16. Kontzias A, Efthimiou P. Adult-onset Still's disease: pathogenesis, clinical manifestations and therapeutic advances. Drugs 2008; 68:319.
  17. Gerfaud-Valentin M, Maucort-Boulch D, Hot A, et al. Adult-onset still disease: manifestations, treatment, outcome, and prognostic factors in 57 patients. Medicine (Baltimore) 2014; 93:91.
  18. Fautrel B. Adult-onset Still disease. Best Pract Res Clin Rheumatol 2008; 22:773.
  19. Gerfaud-Valentin M, Jamilloux Y, Iwaz J, Sève P. Adult-onset Still's disease. Autoimmun Rev 2014; 13:708.
  20. Calabro JJ, Marchesano JM. Fever associated with juvenile rheumatoid arthritis. N Engl J Med 1967; 276:11.
  21. 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; 22:89.
  22. 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; 25:647.
  23. Reginato AJ, Schumacher HR Jr, 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; 17:39.
  24. Ichida H, Kawaguchi Y, Sugiura T, et al. Clinical manifestations of Adult-onset Still's disease presenting with erosive arthritis: Association with low levels of ferritin and Interleukin-18. Arthritis Care Res (Hoboken) 2014; 66:642.
  25. Nguyen KH, Weisman MH. Severe sore throat as a presenting symptom of adult onset Still's disease: a case series and review of the literature. J Rheumatol 1997; 24:592.
  26. Chen DY, Lan HH, Hsieh TY, et al. Crico-thyroid perichondritis leading to sore throat in patients with active adult-onset Still's disease. Ann Rheum Dis 2007; 66:1264.
  27. Esdaile JM, Tannenbaum H, Lough J, Hawkins D. Hepatic abnormalities in adult onset Still's disease. J Rheumatol 1979; 6:673.
  28. Dino O, Provenzano G, Giannuoli G, et al. Fulminant hepatic failure in adult onset Still's disease. J Rheumatol 1996; 23:784.
  29. Cheema GS, Quismorio FP Jr. Pulmonary involvement in adult-onset Still's disease. Curr Opin Pulm Med 1999; 5:305.
  30. Van Hoeyweghen RJ, De Clerck LS, Van Offel JF, Stevens WJ. Interstitial lung disease and adult-onset Still's disease. Clin Rheumatol 1993; 12:418.
  31. Suleiman M, Wolfovitz E, Boulman N, Levy Y. Adult onset Still's disease as a cause of ARDS and acute respiratory failure. Scand J Rheumatol 2002; 31:181.
  32. Manganelli P, Fietta P, Zuccoli P. Adult-onset Still's disease with respiratory distress syndrome, polyserositis and disseminated intravascular coagulation: a case with a fatal outcome. Clin Exp Rheumatol 2003; 21:139.
  33. Drouot MH, Hachulla E, Flipo RM, et al. [Cardiac complication of adult-onset Still's disease: from pericarditis to tamponade, sometimes a manifestation of the disease]. Rev Med Interne 1993; 14:1017.
  34. Valente RM, Banks PM, Conn DL. Characterization of lymph node histology in adult onset Still's disease. J Rheumatol 1989; 16:349.
  35. Quaini F, Manganelli P, Pileri S, et al. Immunohistological characterization of lymph nodes in two cases of adult onset Still's disease. J Rheumatol 1991; 18:1418.
  36. Trotta F, Dovigo L, Scapoli G, et al. Immunoblastic malignant lymphoma in adult onset Still's disease. J Rheumatol 1993; 20:1788.
  37. Arlet JB, Le TH, Marinho A, et al. Reactive haemophagocytic syndrome in adult-onset Still's disease: a report of six patients and a review of the literature. Ann Rheum Dis 2006; 65:1596.
  38. Bae CB, Jung JY, Kim HA, Suh CH. Reactive hemophagocytic syndrome in adult-onset Still disease: clinical features, predictive factors, and prognosis in 21 patients. Medicine (Baltimore) 2015; 94:e451.
  39. Hot A, Toh ML, Coppéré B, et al. Reactive hemophagocytic syndrome in adult-onset Still disease: clinical features and long-term outcome: a case-control study of 8 patients. Medicine (Baltimore) 2010; 89:37.
  40. Bürgi U, Mendez A, Hasler P, Hüllstrung HD. Hemophagocytic syndrome in adult-onset Still's disease (AOSD): a must for biologics?--Case report and brief review of the literature. Rheumatol Int 2012; 32:3269.
  41. Coffernils M, Soupart A, Pradier O, et al. Hyperferritinemia in adult onset Still's disease and the hemophagocytic syndrome. J Rheumatol 1992; 19:1425.
  42. Boki KA, Tsirantonaki MJ, Markakis K, Moutsopoulos HM. Thrombotic thrombocytopenic purpura in adult Still's disease. J Rheumatol 1996; 23:385.
  43. Diamond JR. Hemolytic uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP) complicating adult Still's disease: remission induced with intravenous immunoglobulin G. J Nephrol 1997; 10:253.
  44. Perez MG, Rodwig FR Jr. Chronic relapsing thrombotic thrombocytopenic purpura in adult onset Still's disease. South Med J 2003; 96:46.
  45. Khobragade AK, Chogle AR, Ram RP, et al. Reversible posterior leukoencephalopathy syndrome in a case of adult onset Still's disease with concurrent thrombotic thrombocytopenic purpura: response to high dose immunoglobulin infusions. J Assoc Physicians India 2012; 60:59.
  46. Rogers J, Lacroix L, Durmowitz G, et al. The role of cytokines in the regulation of ferritin expression. Adv Exp Med Biol 1994; 356:127.
  47. Schwarz-Eywill M, Heilig B, Bauer H, et al. Evaluation of serum ferritin as a marker for adult Still's disease activity. Ann Rheum Dis 1992; 51:683.
  48. 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; 21:890.
  49. Akritidis N, Giannakakis I, Giouglis T. Ferritin levels and response to treatment in patients with Adult Still's disease. J Rheumatol 1996; 23:201.
  50. Kumakura S, Ishikura H, Munemasa S, et al. Adult onset Still's disease associated hemophagocytosis. J Rheumatol 1997; 24:1645.
  51. Hamidou MA, Denis M, Barbarot S, et al. Usefulness of glycosylated ferritin in atypical presentations of adult onset Still's disease. Ann Rheum Dis 2004; 63:605.
  52. Vignes S, Le Moël G, Fautrel B, et al. Percentage of glycosylated serum ferritin remains low throughout the course of adult onset Still's disease. Ann Rheum Dis 2000; 59:347.
  53. Fautrel B, Le Moël G, Saint-Marcoux B, et al. Diagnostic value of ferritin and glycosylated ferritin in adult onset Still's disease. J Rheumatol 2001; 28:322.
  54. Chung JW, Suh YJ, Song HJ, et al. Pure red cell aplasia and adult-onset Still's disease. Clin Rheumatol 2004; 23:368.
  55. Min JK, Cho CS, Kim HY, Oh EJ. Bone marrow findings in patients with adult Still's disease. Scand J Rheumatol 2003; 32:119.
  56. 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; 25:396.
  57. Kawashima M, Yamamura M, Taniai M, et al. Levels of interleukin-18 and its binding inhibitors in the blood circulation of patients with adult-onset Still's disease. Arthritis Rheum 2001; 44:550.
  58. Medsger TA Jr, Christy WC. Carpal arthritis with ankylosis in late onset Still's disease. Arthritis Rheum 1976; 19:232.
  59. Björkengren 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; 165:545.
  60. Yamaguchi M, Ohta A, Tsunematsu T, et al. Preliminary criteria for classification of adult Still's disease. J Rheumatol 1992; 19:424.
  61. 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; 49:283.
  62. Ben m'rad M, Leclerc-Mercier S, Blanche P, et al. Drug-induced hypersensitivity syndrome: clinical and biologic disease patterns in 24 patients. Medicine (Baltimore) 2009; 88:131.
  63. Esumi N, Ikushima S, Hibi S, et al. High serum ferritin level as a marker of malignant histiocytosis and virus-associated hemophagocytic syndrome. Cancer 1988; 61:2071.
  64. Lambotte O, Cacoub P, Costedoat N, et al. High ferritin and low glycosylated ferritin may also be a marker of excessive macrophage activation. J Rheumatol 2003; 30:1027.
  65. Cush JJ, Medsger TA Jr, Christy WC, et al. Adult-onset Still's disease. Clinical course and outcome. Arthritis Rheum 1987; 30:186.
  66. Goldman JA, Beard MR, Casey HL. Acute febrile juvenile rheumatoid arthritis in adults: cause of polyarthritis and fever. South Med J 1980; 73:555.
  67. Kahn MF, Delaire M. Maladie de Still de l'adulte. In: Les maladies systemiques, Kahn MF, et al (Eds), Flammarion, Paris 1991.
  68. Fautrel B, Zing E, Golmard JL, et al. Proposal for a new set of classification criteria for adult-onset still disease. Medicine (Baltimore) 2002; 81:194.
  69. Masson C, Le Loet X, Liote F, et al. Comparative study of 6 types of criteria in adult Still's disease. J Rheumatol 1996; 23:495.