{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T07:56:42Z","timestamp":1791619002090,"version":"4.3.4"},"reference-count":175,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2022,10,24]],"date-time":"2022-10-24T00:00:00Z","timestamp":1666569600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Adult-onset Still\u2019s disease (AOSD) is a systemic inflammatory disorder with an unknown cause characterized by high-spiking fever, lymphadenopathy, hepatosplenomegaly, hyperferritinemia, and leukocytosis. The clinical course can be divided into three significant patterns, each with a different prognosis: Self-limited or monophasic, intermittent or polycyclic systemic, and chronic articular. Two criteria sets have been validated. The Yamaguchi criteria are the most generally used, although the Fautrel criteria offer the benefit of adding ferritin and glycosylated ferritin values. AOSD\u2019s pathogenesis is not yet completely understood. Chemokines and pro-inflammatory cytokines, including interferon (IFN)-\u03b3, tumor necrosis factor \u03b1 (TNF\u03b1), interleukin (IL)-1, IL-6, IL-8, and IL-18, play a crucial role in the progression of illness, resulting in the development of innovative targeted therapeutics. There are no treatment guidelines for AOSD due to its rarity, absence of controlled research, and lack of a standard definition for remission and therapy objectives. Non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids (CS), and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) are used in AOSD treatment. Biological therapy, including IL-1, IL-6, IL-18, and IL-17 inhibitors, as well as TNF\u03b1 or Janus-kinases (JAKs) inhibitors, is administered to patients who do not react to CS and csDMARDs or achieve an inadequate response.<\/jats:p>","DOI":"10.3390\/ijms232112810","type":"journal-article","created":{"date-parts":[[2022,10,24]],"date-time":"2022-10-24T10:09:23Z","timestamp":1666606163000},"page":"12810","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Adult-Onset Still\u2019s Disease\u2014A Complex Disease, a Challenging Treatment"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4856-867X","authenticated-orcid":false,"given":"Luana Andreea","family":"Macovei","sequence":"first","affiliation":[{"name":"Department of Rheumatology, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, Romania"},{"name":"Clinical Rehabilitation Hospital, 700661 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7361-4685","authenticated-orcid":false,"given":"Alexandra","family":"Burlui","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, Romania"},{"name":"Clinical Rehabilitation Hospital, 700661 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2784-0937","authenticated-orcid":false,"given":"Ioana","family":"Bratoiu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, Romania"},{"name":"Clinical Rehabilitation Hospital, 700661 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ciprian","family":"Rezus","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"},{"name":"III Internal Medicine Clinic, \u201cSt. Spiridon\u201d County Emergency Clinical Hospital, 700111 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9800-9289","authenticated-orcid":false,"given":"Anca","family":"Cardoneanu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, Romania"},{"name":"Clinical Rehabilitation Hospital, 700661 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Richter","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, Romania"},{"name":"Clinical Rehabilitation Hospital, 700661 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreea","family":"Szalontay","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"},{"name":"Institute of Psychiatry \u201cSocola\u201d, 700282 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Rezus","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, Romania"},{"name":"Clinical Rehabilitation Hospital, 700661 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/s41584-018-0081-x","article-title":"Mechanisms, Biomarkers and Targets for Adult-Onset Still\u2019s Disease","volume":"14","author":"Feist","year":"2018","journal-title":"Nat. Rev. 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