Guideline sources The following summarized guidelines for the evaluation and management of adult-onset Still's disease (ASD) are prepared by our editorial team based on guidelines from the American College of Rheumatology (ACR 2023), the German Society of Rheumatology (DGRh 2022), the European League Against Rheumatism (EULAR 2022), the National Institute for Health and Care Excellence (NICE 2021), the Adult-onset Still's Disease Consensus Group (AOSD-CG 2019), and the Ministry of Health, Labour and Welfare of Japan (MHLW 2018). 1 2 3 4 5 6 Calculator Calculator Fautrel's diagnostic criteria for a Yamaguchi diagnostic criteria fo Guidelines 1. Screening and diagnosis Definition: As per DGRh 2022 guidelines, recognize that ASD is a rare, polygenetic, autoinflammatory disorder. B https://web.pathway.md/diseases/recKXcdSwb7GjDVhL 1/4 6/23/23, 2:12 AM Adult-onset Still's disease Pathway As per AOSD-CG 2019 guidelines: Recognize that ASD and systemic JIA show substantial similarities in terms of clinical manifestations, laboratory features, response to treatment, B and, possibly, genetic background B Consider viewing ASD and systemic JIA as the same disease and attributing differences in the rate of clinical manifestations to the age of onset. C Clinical presentation: as per DGRh 2022 guidelines, recognize that in ASD: arthralgias are very common (> 80%) and arthritis is common (> 50%) a polyarticular course is observed more often than oligo- or monoarticular involvement very commonly involved regions (> 50%) are knees, ankles, and wrists, followed by (> 20%) elbows, shoulders, and fingers. B Show 4 more Diagnostic criteria: Diagnose ASD based on the typical combination of: very common symptoms (> 50%), such as fever > 39 C, rash, arthralgia, arthritis, throat pain, lymphadenopathy, myalgia common symptoms (> 20%), such as splenomegaly, hepatomegaly, weight loss less common characteristic symptoms (< 20%), such as pleuritis, pericarditis, abdominal pain exclusion of alternative rheumatological, hemato-oncological, and infectious diseases. B Consider supporting the clinical diagnosis of ASD by fulfilling the Yamaguchi criteria. C 2. Diagnostic investigations Laboratory testing: As per DGRh 2022 guidelines: Measure serum ferritin levels for diagnosis and follow-up of patients with ASD and to assess disease activity in conjunction with markers of inflammation, such as CRP. Recognize that a markedly elevated serum ferritin level ( 5 ULN) and, if available, markedly reduced fraction of glycosylated ferritin (< 20%) further support the diagnosis of ASD. B Consider measuring IL-18 levels to substantiate the diagnosis and disease activity in patients with ASD. C Evaluation for complications: Evaluate macrophage activation syndrome, a complication of ASD, in case of risk factors such as high clinical disease activity and laboratory markers such as a high ferritin serum level and cytopenia. B Exclude AA amyloidosis, a rare complication of ASD, in case of persistently active disease. B Pretreatment evaluation: screen for HBV infection in all patients eligible for treatment with conventional synthetic, biological, or targeted synthetic DMARDs, immunosuppressants, or corticosteroids (according to dose and duration). B https://web.pathway.md/diseases/recKXcdSwb7GjDVhL 2/4 6/23/23, 2:12 AM Adult-onset Still's disease Pathway Show 3 more 3. Medical management General principles: Ensure rheumatological expertise in diagnosing and treating ASD. B Follow the principles of participatory decision-making within a holistic therapeutic approach including pharmacological therapy alongside accompanying measures such as analgetic and physical therapy, rehabilitative measures, functional training, and the involvement of patient support groups for the treatment of ASD. B Nonsteroidal anti-inflammatory drugs: as per DGRh 2022 guidelines, consider initiating NSAIDs and other analgesics and antipyretics to control symptoms, such as pain and fever. C Corticosteroids: as per DGRh 2022 guidelines, initiate systemic corticosteroids as part of the initial therapy of acute-onset ASD. B Disease-modifying antirheumatic drugs: as per DGRh 2022 guidelines, consider initiating corticosteroid-sparing agents and/or alternative pharmacological therapies to prevent unwanted corticosteroid side effects. C Consider initiating methotrexate or calcineurin inhibitors, especially cyclosporin, as corticosteroid-sparing agents. B Biologics: As per DGRh 2022 guidelines, consider initiating biologics as corticosteroid-sparing agents, such as tocilizumab, B anakinra, B , or canakinumab. B Show 2 more As per NICE 2021 guidelines, initiate anakinra in patients with ASD not responding adequately to 2 conventional DMARDs. E As per AOSD-CG 2019 guidelines: Initiate IL-1 Inhibitors to improve clinical and laboratory parameters and for the significant corticosteroid-sparing effect in patients with ASD refractory to conventional treatment and/or other biologics. B Initiate IL-1 inhibitors for the treatment of ASD-related macrophage activation syndrome, B although cases of macrophage activation syndrome occurring during treatment with these drugs are reported. B 4. Preventative measures Routine immunizations: consider offering high-dose or adjuvanted influenza vaccination, rather than regular-dose influenza vaccination, in 65 years old patients with rheumatic or musculoskeletal diseases and in 18-65 years old patients with rheumatic or musculoskeletal diseases on immunosuppressive medications. C Show 17 more https://web.pathway.md/diseases/recKXcdSwb7GjDVhL 3/4 6/23/23, 2:12 AM Adult-onset Still's disease Pathway Prophylaxis for Pneumocystis jirovecii pneumonia: consider administering prophylaxis against P. jirovecii pneumonia in patients initiating high-dose corticosteroids, especially in combination with immunosuppressants and depending on the risk-benefit ratio. C References 1. Stefan Vordenb umen, Eugen Feist, J rgen Rech et al. Diagnosis and treatment of adult-onset Still's disease: a concise summary of the German society of rheumatology S2 guideline. Z Rheumatol. 2022 Dec 15. Open 2. Toshihide Mimura, Yuya Kondo, Akihide Ohta et al. Evidence-based clinical practice guideline for adult Still's disease. Mod Rheumatol. 2018 Sep;28 5 736 757. Open 3. George E Fragoulis, Elena Nikiphorou, Mrinalini Dey et al. 2022 EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in adults with autoimmune inflammatory rheumatic diseases. Ann Rheum Dis. 2022 Nov 3;ard-2022 223335. Open 4. Anne R Bass, Eliza Chakravarty, Elie A Akl et al. 2022 American College of Rheumatology Guideline for Vaccinations in Patients With Rheumatic and Musculoskeletal Diseases. Arthritis Rheumatol. 2023 Jan 4. Online ahead of print. Open 5. NICE. Anakinra for treating Still s disease. NICE. 2021. Open 6. Serena Colafrancesco, Maria Manara, Alessandra Bortoluzzi 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. Open 7. M Yamaguchi, A Ohta, T Tsunematsu et al. Preliminary criteria for classification of adult Still's disease. J Rheumatol. 1992 Mar;19 3 424 30. Open 8. Bruno Fautrel, Emmanuel Zing, Jean-Louis Golmard et al. Proposal for a new set of classification criteria for adult-onset still disease. Medicine Baltimore). 2002 May;81 3 194 200. Open https://web.pathway.md/diseases/recKXcdSwb7GjDVhL 4/4