Adult-onset Still's disease

Last updated
Adult-onset Still's disease
Specialty Rheumatology
Named after Sir George Frederic Still

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.

Contents

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]

Pathophysiology

The cause of adult-onset Still's disease is unknown and it is not heritable, 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]

Diagnosis

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

Classification

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

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 and polyarticular disease were at higher risk to develop disabling arthritis. [14]

Treatment

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]

Epidemiology

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]

History

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

Related Research Articles

<span class="mw-page-title-main">Arthritis</span> Type of joint disorder

Arthritis is a term often used to mean any disorder that affects joints. Symptoms generally include joint pain and stiffness. Other symptoms may include redness, warmth, swelling, and decreased range of motion of the affected joints. In some types of arthritis, other organs are also affected. Onset can be gradual or sudden.

<span class="mw-page-title-main">Gout</span> Form of arthritis causing swollen joints

Gout is a form of inflammatory arthritis characterized by recurrent attacks of a red, tender, hot, and swollen joint, caused by the deposition of needle-like crystals of uric acid known as monosodium urate crystals. Pain typically comes on rapidly, reaching maximal intensity in less than 12 hours. The joint at the base of the big toe is affected (Podagra) in about half of cases. It may also result in tophi, kidney stones, or kidney damage.

<span class="mw-page-title-main">Sjögren syndrome</span> Autoimmune disease affecting the bodys moisture-producing glands

Sjögren syndrome or Sjögren's syndrome is a long-term autoimmune disease that affects the body's moisture-producing glands, and often seriously affects other organ systems, such as the lungs, kidneys, and nervous system.

Rheumatology is a branch of medicine devoted to the diagnosis and management of disorders whose common feature is inflammation in the bones, muscles, joints, and internal organs. Rheumatology covers more than 100 different complex diseases, collectively known as rheumatic diseases, which includes many forms of arthritis as well as lupus and Sjögren's syndrome. Doctors who have undergone formal training in rheumatology are called rheumatologists.

<span class="mw-page-title-main">Methotrexate</span> Chemotherapy and immunosuppressant medication

Methotrexate (MTX), formerly known as amethopterin, is a chemotherapy agent and immune-system suppressant. It is used to treat cancer, autoimmune diseases, and ectopic pregnancies. Types of cancers it is used for include breast cancer, leukemia, lung cancer, lymphoma, gestational trophoblastic disease, and osteosarcoma. Types of autoimmune diseases it is used for include psoriasis, rheumatoid arthritis, and Crohn's disease. It can be given by mouth or by injection.

<span class="mw-page-title-main">Ankylosing spondylitis</span> Type of arthritis of the spine

Ankylosing spondylitis (AS) is a type of arthritis characterized by long-term inflammation of the joints of the spine, typically where the spine joins the pelvis. With AS, eye and bowel problems, and back pain may occur. Joint mobility in the affected areas sometimes worsens over time. Ankylosing spondylitis is believed to involve a combination of genetic and environmental factors. More than 8% of people affected in the UK have a specific human leukocyte antigen known as the HLA-B27 antigen. The underlying mechanism is believed to be autoimmune or autoinflammatory. Diagnosis is based on symptoms with support from medical imaging and blood tests. AS is a type of seronegative spondyloarthropathy, meaning that tests show no presence of rheumatoid factor (RF) antibodies.

<span class="mw-page-title-main">Anakinra</span> Pharmaceutical drug

Anakinra, sold under the brand name Kineret, is a biopharmaceutical medication used to treat rheumatoid arthritis, cryopyrin-associated periodic syndromes, familial Mediterranean fever, and Still's disease. It is a slightly modified recombinant version of the human interleukin 1 receptor antagonist protein. It is marketed by Swedish Orphan Biovitrum. Anakinra is administered by subcutaneous injection.

Macrophage activation syndrome is a severe, potentially life-threatening, complication of several chronic rheumatic diseases of childhood. It occurs most commonly with systemic-onset juvenile idiopathic arthritis (SoJIA). In addition, MAS has been described in association with systemic lupus erythematosus (SLE), Kawasaki disease, and adult-onset Still's disease. It is thought to be closely related and pathophysiologically very similar to reactive (secondary) hemophagocytic lymphohistiocytosis (HLH). The incidence of MAS is unknown as there is a wide spectrum of clinical manifestations, and episodes may remain unrecognized.

Periodic fever syndromes are a set of disorders characterized by recurrent episodes of systemic and organ-specific inflammation. Unlike autoimmune disorders such as systemic lupus erythematosus, in which the disease is caused by abnormalities of the adaptive immune system, people with autoinflammatory diseases do not produce autoantibodies or antigen-specific T or B cells. Instead, the autoinflammatory diseases are characterized by errors in the innate immune system.

<span class="mw-page-title-main">Hemophagocytic lymphohistiocytosis</span> Immune disorder in the blood leading to hyperinflammation

In hematology, hemophagocytic lymphohistiocytosis (HLH), also known as haemophagocytic lymphohistiocytosis, and hemophagocytic or haemophagocytic syndrome, is an uncommon hematologic disorder seen more often in children than in adults. It is a life-threatening disease of severe hyperinflammation caused by uncontrolled proliferation of benign lymphocytes and macrophages that secrete high amounts of inflammatory cytokines. It is classified as one of the cytokine storm syndromes. There are inherited and non-inherited (acquired) causes of HLH.

<span class="mw-page-title-main">Mevalonate kinase deficiency</span> Medical condition

Mevalonate kinase deficiency (MKD) is an autosomal recessive metabolic disorder that disrupts the biosynthesis of cholesterol and isoprenoids. It is a very rare genetic disease.

Tocilizumab, sold under the brand name Actemra among others, is an immunosuppressive drug, used for the treatment of rheumatoid arthritis, systemic juvenile idiopathic arthritis, a severe form of arthritis in children, and COVID‑19. It is a humanized monoclonal antibody against the interleukin-6 receptor (IL-6R). Interleukin 6 (IL-6) is a cytokine that plays an important role in immune response and is implicated in the pathogenesis of many diseases, such as autoimmune diseases, multiple myeloma and prostate cancer. Tocilizumab was jointly developed by Osaka University and Chugai, and was licensed in 2003 by Hoffmann-La Roche.

<span class="mw-page-title-main">Canakinumab</span> Pharmaceutical drug

Canakinumab, sold under the brand name Ilaris, is a medication for the treatment of systemic juvenile idiopathic arthritis, active Still's disease, including adult-onset Still's disease, gout flares. It is a human monoclonal antibody targeted at interleukin-1 beta. It has no cross-reactivity with other members of the interleukin-1 family, including interleukin-1 alpha.

Schnitzler syndrome or Schnitzler's syndrome is a rare disease characterised by onset around middle age of chronic hives (urticaria) and periodic fever, bone pain and joint pain, weight loss, malaise, fatigue, swollen lymph glands and enlarged spleen and liver.

<span class="mw-page-title-main">Cryopyrin-associated periodic syndrome</span> Medical condition

Cryopyrin-associated periodic syndrome (CAPS) is a group of rare, heterogeneous autoinflammatory disease characterized by interleukin 1β-mediated systemic inflammation and clinical symptoms involving skin, joints, central nervous system, and eyes. It encompasses a spectrum of three clinically overlapping autoinflammatory syndromes including familial cold autoinflammatory syndrome, the Muckle–Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disease that were originally thought to be distinct entities, but in fact share a single genetic mutation and pathogenic pathway, and keratoendotheliitis fugax hereditaria in which the autoinflammatory symptoms affect only the anterior segment of the eye.

Anti-interleukin-6 agents are a class of therapeutics. Interleukin 6 is a cytokine relevant to many inflammatory diseases and many cancers. Hence, anti-IL6 agents have been sought. In rheumatoid arthritis they can help patients unresponsive to TNF inhibitors.

<span class="mw-page-title-main">Secukinumab</span> Monoclonal antibody against IL-17

Secukinumab, sold under the brand name Cosentyx among others, is a human IgG1κ monoclonal antibody used for the treatment of psoriasis, ankylosing spondylitis, and psoriatic arthritis. It binds to the protein interleukin (IL)-17A and is marketed by Novartis.

<span class="mw-page-title-main">Apremilast</span> Medication for psoriasis and psoriatic arthritis

Apremilast, sold under the brand name Otezla among others, is a medication for the treatment of certain types of psoriasis and psoriatic arthritis. The drug acts as a selective inhibitor of the enzyme phosphodiesterase 4 (PDE4) and inhibits spontaneous production of TNF-alpha from human rheumatoid synovial cells. It is taken by mouth.

Systemic juvenile idiopathic arthritis is a type of juvenile idiopathic arthritis (JIA) with extra-articular manifestations like fever and rash apart from arthritis. It was originally called systemic-onset juvenile rheumatoid arthritis or Still's disease.

<span class="mw-page-title-main">Antiarthritics</span> Drug class

An antiarthritic is any drug used to relieve or prevent arthritic symptoms, such as joint pain or joint stiffness. Depending on the antiarthritic drug class, it is used for managing pain, reducing inflammation or acting as an immunosuppressant. These drugs are typically given orally, topically or through administration by injection. The choice of antiarthritic medication is often determined by the nature of arthritis, the severity of symptoms as well as other factors, such as the tolerability of side effects.

References

  1. 1 2 3 4 5 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): 4031–4034. doi:10.1007/s00296-010-1529-8. PMID   20495923. S2CID   19431424.
  2. 1 2 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. 1 2 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. 1 2 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. 1 2 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. 1 2 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.
  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" (PDF). 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. 22 (1). London: 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. S2CID   10549641.
  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.
  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. 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.
  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.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.