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Adult onset Still's disease — Clinical Guidelines

Overview

Adult-onset Still's disease (AOSD) is a rare autoinflammatory disorder characterized by systemic inflammation, fever, rash, and arthritis, often resembling systemic juvenile idiopathic arthritis (sJIA) in clinical manifestations 3 5.

Diagnosis

Clinical Criteria: High fever, evanescent rash, arthritis, and at least one of the following: sore throat, lymphadenopathy, serositis, hepatomegaly/splenomegaly, or polysynovitis 13.

Laboratory Tests: Elevated ferritin, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) 1 6.

Differentiating MAS: Use caution with 2016 EULAR/ACR/PRINTO criteria for macrophage activation syndrome (MAS) in AOSD; applicability may vary 7.

Renal Involvement: Consider renal biopsy for unexplained renal pathology, as mesangial glomerulonephritis can occur 12.

Management

First-Line Treatments:

- Anti-IL-1 Agents: Anakinra (initial dose 100 mg/day SC), canakinumab (single IV dose based on weight), rilonacept (4 mg/kg SC every 2 weeks) 1. - IL-6 Antagonists: Tocilizumab (8 mg/kg IV or 40 mg SC every 2-4 weeks) 1.

Adjunctive Treatments:

- Cyclosporine A: For severe cases with multi-organ failure and disseminated intravascular coagulation (DIC) 11. - Other Immunosuppressants: Consider in refractory cases, though specific dosing not detailed in abstracts 10.

Special Populations

Pregnancy: Limited data; management should focus on balancing maternal and fetal safety with disease control 13.

Comorbidities: Special attention required for organ involvement, particularly renal and hematological complications, necessitating tailored treatment approaches 4 11 12.

Key Recommendations

Use of Biologic Agents: Employ anti-IL-1 agents or IL-6 antagonists as first-line therapy for active AOSD (Evidence: Strong 1).

Monitoring Ferritin Levels: Regular monitoring of ferritin levels to guide treatment and assess disease activity (Evidence: Moderate 6).

Early Recognition of MAS: Early identification and management of macrophage activation syndrome, considering limitations in current diagnostic criteria (Evidence: Moderate 7).

Renal Involvement Evaluation: Perform renal biopsies when there is suspicion of glomerular involvement to guide specific treatment (Evidence: Weak 12).

Multidisciplinary Approach: Manage severe cases requiring intensive care with a multidisciplinary team, including rheumatology, nephrology, and hematology (Evidence: Expert opinion 8).

References

1 Kilic B, Ozturk A, Karup S, Hacioglu E, Ugurlu S. Efficacy and safety of biologic drugs in Still's disease: a systematic review and network meta-analysis of randomized controlled trials. Rheumatology (Oxford, England) 2025. link 2 Friedrich R, Kernder A, Blank N, Ernst D, Henes J, Keyßer G et al.. Implementation of the new DGRh S2e guideline on diagnostics and treatment of adult-onset Still's disease in Germany : Implications for clinical practice in rheumatology. Zeitschrift fur Rheumatologie 2025. link 3 Fautrel B, Mitrovic S, De Matteis A, Bindoli S, Antón J, Belot A et al.. EULAR/PReS recommendations for the diagnosis and management of Still's disease, comprising systemic juvenile idiopathic arthritis and adult-onset Still's disease. Annals of the rheumatic diseases 2024. link 4 Arya PVA, Marnet E, Rondla M, Tan JW, Unnikrishnan D, Buller G. Renal manifestations in adult-onset Still's disease: a systematic review. Rheumatology international 2024. link 5 De Matteis A, Bindoli S, De Benedetti F, Carmona L, Fautrel B, Mitrovic S. Systemic juvenile idiopathic arthritis and adult-onset Still's disease are the same disease: evidence from systematic reviews and meta-analyses informing the 2023 EULAR/PReS recommendations for the diagnosis and management of Still's disease. Annals of the rheumatic diseases 2024. link 6 Onuora S. Ferritin-induced NETs lead to cytokine storm in AOSD. Nature reviews. Rheumatology 2023. link 7 Tada Y, Inokuchi S, Maruyama A, Suematsu R, Sakai M, Sadanaga Y et al.. Are the 2016 EULAR/ACR/PRINTO classification criteria for macrophage activation syndrome applicable to patients with adult-onset Still's disease?. Rheumatology international 2019. link 8 Néel A, Wahbi A, Tessoulin B, Boileau J, Carpentier D, Decaux O et al.. Diagnostic and management of life-threatening Adult-Onset Still Disease: a French nationwide multicenter study and systematic literature review. Critical care (London, England) 2018. link 9 Ames PR, Walker E, Aw D, Marshall D, de Villiers F, Staber M. Multi-organ failure in adult onset Still's disease: a septic disguise. Clinical rheumatology 2009. link 10 Uppal SS, Al-Mutairi M, Hayat S, Abraham M, Malaviya A. Ten years of clinical experience with adult onset Still's disease: is the outcome improving?. Clinical rheumatology 2007. link 11 Park JH, Bae JH, Choi YS, Lee HS, Jun JB, Jung S et al.. Adult-onset Still's disease with disseminated intravascular coagulation and multiple organ dysfunctions dramatically treated with cyclosporine A. Journal of Korean medical science 2004. link 12 Wendling D, Hory B, Blanc D. Adult Still's disease and mesangial glomerulonephritis. Report of two cases. Clinical rheumatology 1990. link 13 Ramanathan M. Adult Still's disease: a missed diagnosis. Singapore medical journal 1989. link 14 Howanietz H, Graninger W. Usefulness of antistreptolysin titre determination in Still's syndrome. Wiener klinische Wochenschrift 1988. link

Adult onset Still's disease