Educational draft · awaiting clinical reviewThe full textbook explains uncertainty but does not replace live national or local guidance, specialist advice, or current prescribing information.
Recognise the fever, rash, arthritis and systemic pattern of adult-onset Still disease, exclude infection and malignancy, identify macrophage activation syndrome, and escalate cytokine-directed therapy with specialist oversight.
Adult-onset Still disease is a rare systemic autoinflammatory disorder. Establish fever timing, rash relation, sore throat, joint symptoms, weight loss, lymph nodes, travel, infection exposure, medicines and malignancy symptoms. Examine during fever if possible and assess joints, skin, liver, spleen, nodes, heart, lungs and neurological state. Classification criteria can structure evidence but do not replace exclusion of dangerous mimics.
Initial tests often show neutrophilic leucocytosis, very high CRP and ESR, anaemia, thrombocytosis and raised liver enzymes. Ferritin may be strikingly raised; glycosylated ferritin is not universally available and no ferritin threshold is diagnostic. RF and ANA help evaluate alternatives. Blood cultures, viral and tuberculosis testing, echocardiography, cross-sectional imaging and tissue or marrow sampling are selected from the phenotype.
Macrophage activation syndrome
Innate immune dysregulation and polygenic susceptibility promote uncontrolled cytokine release without a single diagnostic autoantibody or inherited Mendelian cause.
Viral or other infections may precede onset in some patients, but no organism consistently explains disease and infection must remain a differential.
Drug, viral and environmental events have been reported around onset, but associations are inconsistent and no one transmissible, occupational or medication trigger explains the disease.
Activated macrophages and neutrophils release pyrogenic and inflammatory cytokines, producing quotidian fever, neutrophilia, rash and acute-phase responses.
Persistent cytokine signalling affects joints, liver, lymphoid tissue, serosa and lung, with variable systemic or arthritis-dominant disease.
Uncontrolled T-cell and macrophage activation causes haemophagocytic inflammation, cytopenia, coagulopathy, hepatic injury and potentially fatal multiorgan failure.
High fever spikes with evanescent rash, sore throat, inflammatory arthritis and neutrophilic inflammation form a characteristic but not pathognomonic pattern.
Lymphadenopathy, hepatosplenomegaly, hepatitis, serositis, myocarditis or lung inflammation indicates systemic burden beyond the joints.
Persistent polyarthritis, wrist involvement and erosive change may dominate after fever settles and requires disease-modifying assessment.
Persistent fever with falling cell counts, fibrinogen, coagulopathy, hepatic or neurological deterioration and rising ferritin is an immediate inflammatory emergency.
Endocarditis, abscess, viral infection and tuberculosis can mimic fever, rash and ferritin elevation and must be actively cultured and imaged.
Lymphoma and leukaemia can cause fever, lymphadenopathy, cytopenia and organomegaly and may require marrow or tissue diagnosis.
Vasculitis, lupus, drug reactions and autoinflammatory syndromes may produce overlapping fever, rash and clinically important organ inflammation.
HLH can accompany infection, malignancy or autoimmune disease, so identifying the inflammatory emergency does not establish Still disease as its trigger.
Positive cultures, focal imaging, clonal blood or tissue findings or discordant response redirects diagnosis and prevents hazardous escalation of immunosuppression.
Rapid haemophagocytic inflammation causes cytopenia, liver failure, bleeding, neurological dysfunction, shock and death without immediate specialist treatment.
Persistent synovitis, particularly involving wrists, can cause progressive erosions, ankylosis, deformity and substantial long-term functional disability.
Pericarditis, myocarditis, pleuritis, pulmonary inflammation and hepatitis can become organ-threatening and require urgent critical multidisciplinary care.
Corticosteroids and cytokine inhibitors increase infection, metabolic, bone, hepatic and haematological risks requiring prevention and structured monitoring.
Large elevations support intense inflammation but occur in infection, liver failure, malignancy and MAS, so trajectory and context matter.
ESR can fall as fibrinogen is consumed during MAS even while fever and organ failure worsen, creating dangerous false reassurance.
It may appear during fever and vanish before rounds, making patient photographs and examination during a spike clinically useful.
Systemic fever may settle while chronic arthritis persists, requiring a different outcome measure and steroid-sparing plan.
New infection or malignancy can emerge during immunosuppression, so an established diagnosis does not close future fever assessment.
Diagnosing Still disease from ferritin elevation alone.
Starting major immunosuppression without adequate infection and malignancy assessment.
Missing MAS because ESR falls or platelets remain within the reference range while rapidly declining.
Treating every recurrent fever as a flare in an immunosuppressed patient.
Continuing high-dose glucocorticoids without a steroid-sparing strategy.
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A patient with suspected adult-onset Still disease remains febrile. Platelets and fibrinogen are falling, ferritin and triglycerides are rising, and confusion has developed. What is the best next action?
National guidance is shown before implementation-dependent detail. Typical adult dose examples remain subject to patient factors, contraindications and the live BNF or specialist protocol. Source check completed 27 Aug 2026; clinical approval remains outstanding.
Editorial contact: Doctor’s Passport editorial team. Source-check date is separate from clinical approval. Report a content problem · Content changes
Treatment is specialist-led. Current EULAR/PReS recommendations prioritise early IL-1 or IL-6 inhibition once the diagnosis is established, aiming for inactive disease while avoiding prolonged systemic glucocorticoids. Short glucocorticoid treatment can bridge targeted therapy or control severe organ disease; methotrexate may support a chronic arthritis-dominant phenotype. Monitor infection, neutropenia, liver tests, lipids and agent-specific reproductive or vaccine risks.
Continue parallel infection assessment and monitor glucose, blood pressure, mood, eyes and bone. Use the shortest effective course, prevent opportunistic infection when the regimen warrants it and never stop established prolonged therapy abruptly.
Do not start during active serious infection and do not give live vaccines concurrently. Check neutrophils before treatment, monthly for six months and quarterly thereafter; monitor liver tests and injection reactions. Product information does not recommend routine use in pregnancy, so use specialist reproductive planning and document later-pregnancy exposure for the infant-vaccine team.