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Health condition

Adult-onset Still's disease, fever, ferritin and the biologics that changed the story.

A rare auto-inflammatory disease with a distinctive pattern - and, in 2026, a treatment ladder that goes far beyond steroids alone.

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Why trust this guide

  • 01

    Editorial team

    Written by our editorial team from the UK sources listed on each page.

  • 02

    Sourced from guidance

    Checked against BSR, EULAR and peer-reviewed rheumatology sources you can see at the end.

  • 03

    Current for 2026

    Reflects modern UK practice including IL-1 and IL-6 blockade and emerging JAK inhibitor use.

Key facts

AOSD at a glance.

The essentials, in plain English - what it is, the criteria used to diagnose it and how it is treated in the UK today.

  • What it is

    Adult-onset Still's disease (AOSD) - a rare systemic auto-inflammatory disorder driven by innate immunity and cytokine excess (IL-1, IL-6, IL-18).

  • Classic triad

    Spiking quotidian fever above 39C, arthritis or arthralgia and an evanescent salmon-pink macular rash that appears with the fever.

  • Yamaguchi criteria

    Diagnosis needs 5 criteria including 2 majors, with infection, malignancy and other rheumatological disease excluded first.

  • Ferritin hallmark

    Serum ferritin above 5x normal with a glycosylated fraction below 20% is highly suggestive.

  • Complication to fear

    Macrophage activation syndrome (MAS) - a life-threatening cytokine storm needing intensive care and IL-1 blockade.

  • Modern treatment

    IL-1 blockade (anakinra, canakinumab) and IL-6 blockade (tocilizumab) have transformed outcomes beyond steroids alone.

Why this guide matters

A rare disease with a distinctive fingerprint.

AOSD is uncommon, and it can look like sepsis, lymphoma or lupus in the early days. Recognising the pattern quickly changes outcomes.

  • Diagnosis is by pattern, not test

    Yamaguchi criteria pull together fever, rash, arthritis and bloods - once infection, malignancy and other rheumatology are excluded.

  • Ferritin is the biochemical clue

    A level above 5x normal with a low glycosylated fraction below 20% strongly supports AOSD over most mimics.

  • Biologics have changed outcomes

    IL-1 and IL-6 blockade reduce flares, spare steroids and, in MAS, can be life-saving.

How the diagnosis is made

From spiking fever to a confirmed diagnosis.

The steps a UK rheumatology team will typically follow, in order - so you know what to expect and why.

  1. 01

    Recognising

    History and fever pattern

    Daily (quotidian) fever spikes above 39C, often evening, resolving spontaneously - with rash and joint pain that come and go with the temperature.

  2. 02

    Recognising

    Rash and joint examination

    Look for the classic evanescent salmon-pink macular rash on trunk and limbs, plus arthritis (wrists, knees, ankles) and sore throat.

  3. 03

    Recognising

    Screening bloods

    FBC (leukocytosis above 10 with neutrophils above 80%), CRP and ESR (very high), LFTs (transaminitis common) and serum ferritin.

  4. 04

    Excluding

    Ferritin and glycosylated fraction

    Ferritin above 5x normal supports AOSD. A glycosylated ferritin fraction below 20% is a strong biochemical fingerprint.

  5. 05

    Excluding

    Exclude mimics

    Blood cultures, viral serology, autoimmune screen (ANA, RF negative in AOSD), CT chest and abdomen to rule out infection, lymphoma and solid tumours.

  6. 06

    Monitoring

    Apply Yamaguchi criteria

    At least 5 criteria including 2 majors (fever, arthritis, rash, leukocytosis) plus minors (sore throat, lymphadenopathy, hepatosplenomegaly, abnormal LFTs, negative ANA and RF).

  7. 07

    Monitoring

    MAS surveillance

    Watch for falling counts, rising ferritin above 10,000, hypofibrinogenaemia, high triglycerides and organ dysfunction - triggers for urgent escalation.

Typical timeline: days to weeks from presentation to confirmed diagnosis and a treatment plan.

Symptoms

What AOSD actually looks like.

The classic triad of fever, rash and arthritis - plus the systemic features that support the diagnosis. And the ones that mean it is time to escalate.

  • Quotidian spiking fever

    Once (sometimes twice) daily temperature spikes above 39C that resolve to normal or below - a hallmark pattern.

  • Salmon-pink evanescent rash

    Macular pink rash on trunk and limbs that appears with the fever and fades between spikes. Can be Koebner-positive.

  • Arthritis and arthralgia

    Symmetrical inflammatory joint pain and swelling - wrists, knees, ankles and small joints. Can become chronic and destructive.

  • Sore throat

    A prominent early symptom - non-exudative pharyngitis that often precedes the systemic features by days or weeks.

  • Lymphadenopathy and hepatosplenomegaly

    Reactive nodes, enlarged liver and spleen - common enough to be part of the Yamaguchi minor criteria.

  • Abnormal liver function

    Transaminitis is very common. Rarely, fulminant hepatitis develops and needs urgent hepatology input.

  • Serositis

    Pericarditis and pleuritis can occur - chest pain, breathlessness or a rub on examination.

  • Red flag - MAS features

    Persistent fever, falling counts, hyperferritinaemia above 10,000, low fibrinogen and organ failure - a rheumatology emergency.

Treatment

How AOSD is treated in the UK.

NSAIDs and corticosteroids first, methotrexate to spare steroids, and IL-1 or IL-6 biologics for systemic or persistent disease. JAK inhibitors and rescue options for refractory cases.

  • NSAIDs

    Useful for mild disease and symptom relief but rarely enough on their own. A diagnostic and bridging role while investigations are completed.

  • High-dose corticosteroids

    First-line for active systemic disease - prednisolone 0.5 to 1 mg/kg daily, tapered as inflammation settles. IV methylprednisolone for severe flares.

  • Methotrexate

    The most common steroid-sparing agent - useful when arthritis dominates and to reduce cumulative steroid burden.

  • Anakinra (IL-1 blockade)

    Daily subcutaneous IL-1 receptor antagonist with rapid onset. First-choice biologic, especially in systemic disease and MAS.

  • Canakinumab (IL-1 blockade)

    Monthly IL-1 beta monoclonal antibody - licensed for AOSD and useful when a longer-acting option suits the patient.

  • Rilonacept (IL-1 blockade)

    Weekly IL-1 trap. Used in selected cases where anakinra or canakinumab are unsuitable.

  • Tocilizumab (IL-6 blockade)

    IV or subcutaneous IL-6 receptor blocker - effective for chronic articular disease and steroid-refractory systemic disease.

  • JAK inhibitors

    Tofacitinib and baricitinib are emerging options for refractory disease - growing evidence but still off-label for AOSD in the UK.

Rescue therapy for MAS

Refractory macrophage activation syndrome may need rituximab, cyclosporine or IVIg alongside high-dose steroids and IL-1 blockade with anakinra. Care is coordinated between rheumatology, haematology and intensive care.

What this guide is based on

The sources behind every claim on this page.

UK and international rheumatology guidance and the diagnostic criteria that shape everyday care, current at the time of last review.

Key references

Guidelines and criteria we relied on.

A quiet reminder

This guide is for information, not medical advice.

Your rheumatology team knows your history and can tell you which parts apply to you. If in doubt, get seen.

  • British Society for Rheumatology (BSR). Guidance on the management of adult-onset Still's disease.

  • EULAR/PReS. Points to consider for the diagnosis and management of Still's disease across the age spectrum.

  • Yamaguchi M et al. Preliminary criteria for classification of adult Still's disease. J Rheumatol 1992.

  • HLH Steering Committee. Diagnostic criteria for macrophage activation syndrome (HScore, 2016 EULAR/ACR).

Red flags

When AOSD needs urgent attention.

Most flares are handled with a planned change in treatment. These are the situations that are not - and where same-day specialist input is essential.

  • Macrophage activation syndrome

    Persistent fever with falling counts, hyperferritinaemia above 10,000, low fibrinogen and rising triglycerides - a life-threatening cytokine storm needing intensive care.

  • Fulminant hepatitis

    Rapidly rising transaminases, jaundice and coagulopathy - requires urgent hepatology and rheumatology input.

  • Cardiac tamponade

    Large pericardial effusion with haemodynamic compromise - a rare but reported complication of severe serositis.

  • Diffuse alveolar haemorrhage

    New breathlessness, haemoptysis and falling haemoglobin - a pulmonary emergency in severe AOSD.

  • Thromboembolic disease

    Active systemic inflammation raises VTE risk - low threshold for imaging when calf pain or breathlessness appear.

  • Steroid toxicity

    Cumulative high-dose steroids drive osteoporosis, diabetes and infection - a strong reason to add a steroid-sparing biologic early.

  • Serious infection on biologics

    IL-1 and IL-6 blockade blunt the febrile response - any suspected infection deserves urgent review.

  • Amyloidosis

    Long-standing uncontrolled inflammation can cause AA amyloid - screen with urine protein and renal function periodically.

  • Undiagnosed malignancy

    Lymphoma can mimic AOSD closely - re-visit imaging and biopsy if the picture is atypical or does not respond to standard treatment.

Living with it

A serious disease, with a treatable trajectory.

Four things that make the biggest difference day to day - watching the right blood tests, staying on top of vaccines, protecting your bones and knowing your MAS red flags.

A quiet reminder

Early biologic control changes the long game.

Reducing cumulative steroid exposure, controlling systemic inflammation and preventing joint damage all follow from getting to the right treatment early.

  1. 01 Monitor

    Track ferritin and CRP

    These are your two most useful biochemical dials. Sudden rises can precede a flare - share the numbers with your rheumatology team.

  2. 02 Vaccinate

    Get the recommended jabs

    Before starting a biologic, complete pneumococcal, seasonal flu and COVID vaccination. Live vaccines are usually avoided while on IL-1 or IL-6 blockade.

  3. 03 Bones

    Protect against steroid harm

    Calcium, vitamin D and a bone-protection plan matter when steroids are needed. Ask about DEXA scanning.

  4. 04 Escalate

    Know your MAS warning signs

    Prolonged fever, easy bruising, breathlessness or rapidly rising ferritin all deserve same-day contact with the on-call rheumatology team.

Frequently asked

Everything we get asked about AOSD.

Quick answers on diagnosis, ferritin, MAS, biologics and long-term outlook.

  • What is adult-onset Still's disease?

    AOSD is a rare systemic auto-inflammatory disease driven by innate immune activation and excess cytokine signalling (IL-1, IL-6, IL-18). It typically presents with daily fever spikes, an evanescent salmon-pink rash and arthritis, alongside very high inflammatory markers and ferritin.

  • How is AOSD diagnosed?

    There is no single test. The Yamaguchi criteria are the most widely used - at least 5 features including 2 majors (fever above 39C for a week, arthralgia for two weeks, typical rash, leukocytosis above 10 with 80% neutrophils) plus minors (sore throat, lymphadenopathy, hepatosplenomegaly, abnormal LFTs, negative ANA and RF). Infection, malignancy and other rheumatological diseases must be excluded first.

  • Why does ferritin matter so much?

    Ferritin is an acute-phase protein but in AOSD it rises far higher than in most other conditions - typically more than five times the upper limit. A low glycosylated ferritin fraction (below 20%) is a useful biochemical fingerprint that helps separate AOSD from other causes of hyperferritinaemia.

  • What is macrophage activation syndrome?

    MAS is a life-threatening cytokine storm that can complicate AOSD. Features include persistent fever, cytopenias, hepatosplenomegaly, hyperferritinaemia (often above 10,000), high triglycerides and low fibrinogen. It needs prompt recognition, intensive care and rapid IL-1 blockade with anakinra, sometimes with cyclosporine, rituximab or IVIg.

  • How is AOSD treated?

    NSAIDs and high-dose corticosteroids are first-line for control. Methotrexate is added as a steroid-sparing agent for chronic arthritis. IL-1 blockade (anakinra, canakinumab, rilonacept) and IL-6 blockade (tocilizumab) are the mainstays of modern biologic care. JAK inhibitors such as tofacitinib and baricitinib are emerging options in refractory disease.

  • Is AOSD lifelong?

    Course varies. Around a third of patients have a self-limiting illness, a third have a relapsing-remitting pattern and a third develop chronic disease dominated by arthritis. Early biologic therapy has improved long-term outcomes and reduced steroid dependence.

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