Adult-onset Still's disease

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Adult-onset Still's disease

Adult-onset Still's disease (AOSD) is a form of Still's disease, a rare systemic autoinflammatory disease characterized by the classic triad of fevers, joint pain, and a distinctive salmon-colored bumpy rash. The disease is considered a diagnosis of exclusion.[1] Levels of the iron-binding protein ferritin may be extremely elevated with this disorder. AOSD may present in a similar manner to other inflammatory diseases and to autoimmune diseases, which must be ruled out before making the diagnosis.

Prognosis is usually favorable but manifestations of the disease affecting the lungs, heart, or kidneys may occasionally cause severe life-threatening complications.[2] It is treated first with corticosteroids such as prednisone. Medications that block the action of interleukin-1, such as anakinra, can be effective treatments when standard steroid treatments are insufficient.[3]

Obvious similarities exist with juvenile rheumatoid arthritis (also known as "juvenile-onset Still's disease"),[4] and there is some evidence that the two conditions are closely related.[5][6]

Signs and symptoms

The disease typically presents with joint pain, high fevers, a salmon-pink macular or maculopapular rash, enlargement of the liver and spleen, swollen lymph nodes, and a neutrophil-predominant increased white blood cell count in the blood.[1] Tests for rheumatoid factor and anti-nuclear antibodies are usually negative and serum ferritin is markedly elevated. Patients experiencing a flare-up from Adult-onset Still's disease usually report extreme fatigue, swelling of the lymph nodes and, less commonly, fluid accumulation in the lungs and heart. In rare cases, AOSD can cause life-threatening complications, including hemophagocytic lymphohistiocytosis, IVDC, fulminant hepatitis, or disabling conditions such as aseptic meningitis and sensorineural hearing loss.[7][8][9][1]


The cause of adult-onset Still's disease is unknown, but it presumably involves interleukin-1 (IL-1), since medications that block the action of IL-1β are effective treatments. Interleukin-18 is expressed at high levels.[2][10][11]


CXCL10 (a, b), CXCL13 (c, d), and CXCR3 (e, f) expression in inflammatory cells in skin biopsy material of individuals with adult-onset Still’s disease

The diagnosis is clinical, not based upon serology.[12] At least seven sets of diagnostic criteria have been devised, however the Yamaguchi criteria have the highest sensitivity. Diagnosis requires at least five features, with at least two of these being major diagnostic criteria.[13]

Major criteria Minor criteria
Fever of at least 39 °C for at least one week Sore throat
Arthralgias or arthritis for at least two weeks Lymphadenopathy
Nonpruritic salmon-colored rash (usually over trunk or extremities while febrile) Hepatomegaly or splenomegaly
Leukocytosis (10,000/microL or greater), with granulocyte predominance Abnormal liver function tests
Negative tests for antinuclear antibody and rheumatoid factor


People with AOSD generally experience one of two patterns in the disease:

  • a debilitating pattern of fevers, pain, and other systemic symptoms, or
  • a somewhat less aggressive pattern, in which the main symptom is arthritis and chronic joint pain.[3]

One set of 21 adult-onset Still's disease patients were divided into four types, according to clinical course patterns. These included monocyclic systemic disease, polycyclic systemic disease, chronic articular monocyclic systemic disease, and chronic articular polycyclic systemic disease. People with chronic articular disease and polyarticular disease were at higher risk to develop disabling arthritis.[14]


Adult-onset Still's disease is treated with anti-inflammatory medications. Steroids such as prednisone are used to treat severe symptoms of Still's. Other commonly used medications include hydroxychloroquine, penicillamine, azathioprine, methotrexate, etanercept, anakinra, tocilizumab, cyclophosphamide, adalimumab, rituximab, and infliximab.[15]

Newer medications target interleukin-1 (IL-1), particularly IL-1β.[16] A randomized, multicenter trial reported better outcomes in a group of 12 patients treated with anakinra than in a group of 10 patients taking other disease-modifying antirheumatic drugs.[17] In June 2020 FDA approved Ilaris (canakinumab) for the treatment of AOSD, this is the first FDA approved treatment for AOSD.[18] Canakinumab is another anti-IL1 drug which selectively binds IL-1β and rilonacept which blocks both IL-1A and IL-1β.[19] The monoclonal anti-IL6 antibody tocilizumab is another treatment option as effective as anakinra.[20]

The condition "juvenile-onset Still's disease" is now usually grouped under juvenile rheumatoid arthritis. However, there are obvious similarities between the two conditions,[4] and there is some evidence that they may be closely related.[5][6]


Adult-onset Still's Disease is rare and has been described all over the world. The number of new cases per year is estimated to be 1.6 per 1,000,000 population.[1] The number of people currently affected is estimated at 1.5 cases per 100,000–1,000,000 population.[citation needed] Onset is most common in two age ranges, between ages 16–25 and between ages of 36–46 years.[21]


Still's disease is named after English physician Sir George Frederic Still (1861–1941).[22][23] The adult-onset version was characterized by E. G. Bywaters in 1971.[1]

Research directions

Researchers are investigating whether levels of a protein named calprotectin could be used to improve diagnosis and monitoring.[24]

See also


  1. 1.0 1.1 1.2 1.3 1.4 Akkara Veetil BM, Yee AH, Warrington KJ, Aksamit AJ Jr, Mason TG (December 2012). "Aseptic meningitis in adult onset Still's disease". Rheumatol Int. 32 (12): 4031–4. doi:10.1007/s00296-010-1529-8. PMID 20495923. S2CID 19431424.
  2. 2.0 2.1 Colafrancesco, Serena; Priori, Roberta; Alessandri, Cristiano; Perricone, Carlo; Pendolino, Monica; Picarelli, Giovanna; Valesini, Guido (2012). "IL-18 Serum Level in Adult Onset Still's Disease: A Marker of Disease Activity". International Journal of Inflammation. 2012: 1–6. doi:10.1155/2012/156890. PMC 3385601. PMID 22762008.
  3. 3.0 3.1 Gerfaud-Valentin, Mathieu; Jamilloux, Yvan; Iwaz, Jean; Sève, Pascal (July 2014). "Adult-onset Still's disease". Autoimmunity Reviews. 13 (7): 708–722. doi:10.1016/j.autrev.2014.01.058. ISSN 1873-0183. PMID 24657513.
  4. 4.0 4.1 Feist E, Mitrovic S, Fautrel B (2018). "Mechanisms, biomarkers and targets for adult-onset Still's disease". Nature Reviews. Rheumatology. 14 (10): 603–618. doi:10.1038/s41584-018-0081-x. PMC 7097309. PMID 30218025.
  5. 5.0 5.1 Vastert SJ, Jamilloux Y, Quartier P, Ohlman S, Osterling Koskinen L, Kullenberg T, Franck-Larsson K, Fautrel B, de Benedetti F (2019). "Anakinra in children and adults with Still's disease". Rheumatology. 58 (Suppl 6): vi9–vi22. doi:10.1093/rheumatology/kez350. PMC 6878842. PMID 31769856.
  6. 6.0 6.1 Jamilloux Y, Georgin-Lavialle S, Sève P, Belot A, Fautrel B (2019). "[It is time to reconcile systemic juvenile idiopathic arthritis and adult-onset Still's disease]". Revue de Médecine Interne (in French). 40 (10): 635–636. doi:10.1016/j.revmed.2019.06.001. PMID 31221454.{{cite journal}}: CS1 maint: unrecognized language (link)
  7. Fauter, M.; Gerfaud-Valentin, M.; Delplanque, M.; Georgin-Lavialle, S.; Sève, P.; Jamilloux, Y. (2020-01-07). "[Adult-onset Still's disease complications]". La Revue de Médecine Interne. 41 (3): 168–179. doi:10.1016/j.revmed.2019.12.003. ISSN 1768-3122. PMID 31924392.
  8. Mitrovic, Stéphane; Fautrel, Bruno (2018). "Complications of adult-onset Still's disease and their management". Expert Review of Clinical Immunology. 14 (5): 351–365. doi:10.1080/1744666X.2018.1465821. ISSN 1744-8409. PMID 29658384. S2CID 4895740.
  9. Néel, Antoine; Wahbi, Anaïs; Tessoulin, Benoit; Boileau, Julien; Carpentier, Dorothée; Decaux, Olivier; Fardet, Laurence; Geri, Guillaume; Godmer, Pascal; Goujard, Cécile; Maisonneuve, Hervé (2018-04-11). "Diagnostic and management of life-threatening Adult-Onset Still Disease: a French nationwide multicenter study and systematic literature review". Critical Care (London, England). 22 (1): 88. doi:10.1186/s13054-018-2012-2. ISSN 1466-609X. PMC 5896069. PMID 29642928.
  10. Sugiura, T; Kawaguchi, Y; Harigai, M; Terajima-Ichida, H; Kitamura, Y; Furuya, T; Ichikawa, N; Kotake, S; Tanaka, M; Hara, M; Kamatani, N (Nov 2002). "Association between adult-onset Still's disease and interleukin-18 gene polymorphisms". Genes and Immunity. 3 (7): 394–9. doi:10.1038/sj.gene.6363922. PMID 12424620.
  11. Jamilloux, Y; Gerfaud-Valentin, M; Martinon, F; Belot, A; Henry, T; Sève, P (February 2015). "Pathogenesis of adult-onset Still's disease: new insights from the juvenile counterpart" (PDF). Immunologic Research. 61 (1–2): 53–62. doi:10.1007/s12026-014-8561-9. PMID 25388963. S2CID 44588159. Archived (PDF) from the original on 2022-05-17. Retrieved 2022-09-18.
  12. Efthimiou P, Kontzias A, Ward CM, Ogden NS (June 2007). "Adult-onset Still's disease: can recent advances in our understanding of its pathogenesis lead to targeted therapy?". Nat Clin Pract Rheumatol. 3 (6): 328–35. doi:10.1038/ncprheum0510. PMID 17538564. S2CID 30465113.
  13. Yamaguchi M, Ohta A, Tsunematsu T, Kasukawa R, Mizushima Y, Kashiwagi H, Kashiwazaki S, Tanimoto K, Matsumoto Y, Ota T (1992). "Preliminary criteria for classification of adult Still's disease". J. Rheumatol. 19 (3): 424–30. PMID 1578458.
  14. Cush, JJ; Medsger TA Jr; Christy, WC; Herbert, DC; Cooperstein, LA (Feb 1987). "Adult-onset Still's disease. Clinical course and outcome". Arthritis and Rheumatism. 30 (2): 186–194. doi:10.1002/art.1780300209. PMID 3827959.
  15. Jamilloux, Y; Gerfaud-Valentin, M; Henry, T; Sève, P (22 December 2014). "Treatment of adult-onset Still's disease: a review". Therapeutics and Clinical Risk Management. 11: 33–43. doi:10.2147/TCRM.S64951. PMC 4278737. PMID 25653531.
  16. Vastert, Sebastiaan J.; Jamilloux, Yvan; Quartier, Pierre; Ohlman, Sven; Osterling Koskinen, Lisa; Kullenberg, Torbjörn; Franck-Larsson, Karin; Fautrel, Bruno; de Benedetti, Fabrizio (2019-11-01). "Anakinra in children and adults with Still's disease". Rheumatology. 58 (Supplement_6): vi9–vi22. doi:10.1093/rheumatology/kez350. ISSN 1462-0332. PMC 6878842. PMID 31769856.
  17. Nordström D; Knight A; Luukkainen R; van Vollenhoven R; et al. (Oct 2012). "Beneficial effect of interleukin 1 inhibition with anakinra in adult-onset Still's disease. An open, randomized, multicenter study". J. Rheumatol. 39 (10): 2008–11. doi:10.3899/jrheum.111549. PMID 22859346. S2CID 207614974.
  18. Commissioner, Office of the (2020-06-16). "FDA Approves First Treatment for Adult Onset Still's Disease, a Severe and Rare Disease". FDA. Archived from the original on 2020-06-17. Retrieved 2020-06-21.
  19. Cecilia Giampietro; Bruno Fautrel (2012). "Review Article: Anti-Interleukin-1 Agents in Adult Onset Still's Disease". International Journal of Inflammation. 2012 (317820): 317820. doi:10.1155/2012/317820. PMC 3350963. PMID 22611515.
  20. Al-Homood, I. A. (2014-01-01). "Biologic treatments for adult-onset Still's disease". Rheumatology. 53 (1): 32–38. doi:10.1093/rheumatology/ket250. ISSN 1462-0324. PMID 23864171.
  21. Owlia MB, Mehrpoor G (2009). "Adult – onset Still's disease : A review" (PDF). Indian J Med Sci. 63 (5): 207–21. doi:10.4103/0019-5359.53169. PMID 19584494. Archived (PDF) from the original on 2018-07-22. Retrieved 2022-09-18.
  22. synd/1773 at Who Named It?
  23. G. F. Still. A special form of joint disease met with in children. Doctoral dissertation, Cambridge, 1896.
  24. Kopeć-Mędrek, Magdalena; Widuchowska, Małgorzata; Kucharz, Eugeniusz J. (2016). "Calprotectin in rheumatic diseases: a review". Reumatologia. 54 (6): 306–309. doi:10.5114/reum.2016.64907. ISSN 0034-6233. PMC 5241367. PMID 28115781.

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