Adult-onset Still's disease

Adult-onset Still’s disease (AOSD) is a rare multi-system autoinflammatory disorder that typically affects young adults. The clinical course varies and can be monocyclic, polycyclic, or chronic with either systemic or articular symptoms predominant.

The diagnosis is challenging as there is no definitive test and the clinical features overlap with those of many other conditions. The classic presenting symptoms are daily intermittent high fevers, arthralgia, and a salmon-pink skin rash, although other symptoms such as pharyngitis are also common. Occasionally, the first presentation may be a life-threatening complication such as macrophage activation syndrome.

It is vital to order a wide range of tests to rule out infection, malignancy, and other rheumatic disorders that can mimic AOSD. If AOSD is then suspected, the key investigations are serum ferritin (hyperferritinaemia is a highly sensitive but poorly specific marker) and, if available, glycosylated ferritin (which is more specific).

Treatment is stepwise, starting with systemic corticosteroids. If the patient does not respond or responds but then relapses when the corticosteroid is tapered, conventional synthetic disease-modifying antirheumatic drugs and/or biological agents can be used as corticosteroid-sparing agents.

AOSD is a rare autoinflammatory condition that usually affects young adults and typically presents with intermittent high-spiking fevers, arthralgias/arthritis, a transient salmon-pink rash, and sore throat among other symptoms.[1]Giacomelli R, Ruscitti P, Shoenfeld Y. A comprehensive review on adult onset Still's disease. J Autoimmun. 2018 Sep;93:24-36. https://www.doi.org/10.1016/j.jaut.2018.07.018 http://www.ncbi.nlm.nih.gov/pubmed/30077425?tool=bestpractice.com [2]Vordenbäumen S, Feist E, Rech J, et al. Diagnosis and treatment of adult-onset Still's disease: a concise summary of the German society of rheumatology S2 guideline. Z Rheumatol. 2023 Feb;82(suppl 2):81-92. https://www.doi.org/10.1007/s00393-022-01294-2 http://www.ncbi.nlm.nih.gov/pubmed/36520170?tool=bestpractice.com [3]Colafrancesco S, Manara M, Bortoluzzi A, et al. Management of adult-onset Still's disease with interleukin-1 inhibitors: evidence- and consensus-based statements by a panel of Italian experts. Arthritis Res Ther. 2019 Dec 11;21(1):275. https://www.doi.org/10.1186/s13075-019-2021-9 http://www.ncbi.nlm.nih.gov/pubmed/31829244?tool=bestpractice.com [4]Macovei LA, Burlui A, Bratoiu I, et al. Adult-onset Still's disease-a complex disease, a challenging treatment. Int J Mol Sci. 2022 Oct 24;23(21):12810. https://www.doi.org/10.3390/ijms232112810 http://www.ncbi.nlm.nih.gov/pubmed/36361602?tool=bestpractice.com [5]Efthimiou P, Kontzias A, Hur P, et al. Adult-onset Still's disease in focus: clinical manifestations, diagnosis, treatment, and unmet needs in the era of targeted therapies. Semin Arthritis Rheum. 2021 Aug;51(4):858-74. https://www.doi.org/10.1016/j.semarthrit.2021.06.004 http://www.ncbi.nlm.nih.gov/pubmed/34175791?tool=bestpractice.com ​​​​​ It is a clinical diagnosis based on the presence of typical symptoms, signs, and investigation results after exclusion of other rheumatological conditions, infections, and malignancy.[2]Vordenbäumen S, Feist E, Rech J, et al. Diagnosis and treatment of adult-onset Still's disease: a concise summary of the German society of rheumatology S2 guideline. Z Rheumatol. 2023 Feb;82(suppl 2):81-92. https://www.doi.org/10.1007/s00393-022-01294-2 http://www.ncbi.nlm.nih.gov/pubmed/36520170?tool=bestpractice.com [4]Macovei LA, Burlui A, Bratoiu I, et al. Adult-onset Still's disease-a complex disease, a challenging treatment. Int J Mol Sci. 2022 Oct 24;23(21):12810. https://www.doi.org/10.3390/ijms232112810 http://www.ncbi.nlm.nih.gov/pubmed/36361602?tool=bestpractice.com [5]Efthimiou P, Kontzias A, Hur P, et al. Adult-onset Still's disease in focus: clinical manifestations, diagnosis, treatment, and unmet needs in the era of targeted therapies. Semin Arthritis Rheum. 2021 Aug;51(4):858-74. https://www.doi.org/10.1016/j.semarthrit.2021.06.004 http://www.ncbi.nlm.nih.gov/pubmed/34175791?tool=bestpractice.com ​​​ Its clinical course is variable with some patients having one or intermittent flares of systemic symptoms followed by periods of remission and others having chronic symptoms that predominantly affect the joints.[2]Vordenbäumen S, Feist E, Rech J, et al. Diagnosis and treatment of adult-onset Still's disease: a concise summary of the German society of rheumatology S2 guideline. Z Rheumatol. 2023 Feb;82(suppl 2):81-92. https://www.doi.org/10.1007/s00393-022-01294-2 http://www.ncbi.nlm.nih.gov/pubmed/36520170?tool=bestpractice.com [4]Macovei LA, Burlui A, Bratoiu I, et al. Adult-onset Still's disease-a complex disease, a challenging treatment. Int J Mol Sci. 2022 Oct 24;23(21):12810. https://www.doi.org/10.3390/ijms232112810 http://www.ncbi.nlm.nih.gov/pubmed/36361602?tool=bestpractice.com [5]Efthimiou P, Kontzias A, Hur P, et al. Adult-onset Still's disease in focus: clinical manifestations, diagnosis, treatment, and unmet needs in the era of targeted therapies. Semin Arthritis Rheum. 2021 Aug;51(4):858-74. https://www.doi.org/10.1016/j.semarthrit.2021.06.004 http://www.ncbi.nlm.nih.gov/pubmed/34175791?tool=bestpractice.com ​​ Some patients present with life-threatening complications, the most common of which is macrophage activation syndrome (MAS).[2]Vordenbäumen S, Feist E, Rech J, et al. Diagnosis and treatment of adult-onset Still's disease: a concise summary of the German society of rheumatology S2 guideline. Z Rheumatol. 2023 Feb;82(suppl 2):81-92. https://www.doi.org/10.1007/s00393-022-01294-2 http://www.ncbi.nlm.nih.gov/pubmed/36520170?tool=bestpractice.com  AOSD is commonly understood to be the adult form of systemic juvenile idiopathic arthritis (sJIA).[3]Colafrancesco S, Manara M, Bortoluzzi A, et al. Management of adult-onset Still's disease with interleukin-1 inhibitors: evidence- and consensus-based statements by a panel of Italian experts. Arthritis Res Ther. 2019 Dec 11;21(1):275. https://www.doi.org/10.1186/s13075-019-2021-9 http://www.ncbi.nlm.nih.gov/pubmed/31829244?tool=bestpractice.com [5]Efthimiou P, Kontzias A, Hur P, et al. Adult-onset Still's disease in focus: clinical manifestations, diagnosis, treatment, and unmet needs in the era of targeted therapies. Semin Arthritis Rheum. 2021 Aug;51(4):858-74. https://www.doi.org/10.1016/j.semarthrit.2021.06.004 http://www.ncbi.nlm.nih.gov/pubmed/34175791?tool=bestpractice.com [6]Al-Hakim A, Mistry A, Savic S. Improving diagnosis and clinical management of acquired systemic autoinflammatory diseases. J Inflamm Res. 2022;15:5739-55. https://www.doi.org/10.2147/JIR.S343261 http://www.ncbi.nlm.nih.gov/pubmed/36238769?tool=bestpractice.com