Adult-Onset Still Disease
On this page
Direct answer
A quotidian fever spiking above 39°C every evening with a salmon-coloured rash that appears only with the spike, arthralgias and a neutrophil leucocytosis, in a patient whose cultures and serologies are repeatedly negative, is the classic picture of adult-onset Still disease (AOSD). Diagnosis uses the Yamaguchi criteria, which demand exclusion of infection, malignancy and other rheumatic disease, and the serum ferritin is characteristically very high, often several thousand ng/mL, with a glycosylated fraction of 20 per cent or less. Treatment escalates from NSAIDs and glucocorticoids to methotrexate and to IL-1 blockade with anakinra, which is often dramatically effective.
What you must remember
- Yamaguchi major criteria: fever 39°C or more lasting a week or more, arthralgia or arthritis lasting two weeks or more, the typical non-pruritic salmon rash, and a leucocyte count of 10,000 per microlitre or more with at least 80 per cent neutrophils.
- Yamaguchi minor criteria: sore throat at onset, lymphadenopathy or splenomegaly, liver enzyme abnormalities, and negative rheumatoid factor and antinuclear antibody; five criteria with at least two major classify the disease.
- The rash is evanescent, salmon-pink, non-pruritic and typically trunk and proximal limb; it may be visible only during fever spikes, so examine at the peak.
- Ferritin is markedly raised (commonly above 1000 ng/mL, sometimes above 10,000) and a glycosylated ferritin of 20 per cent or less supports the diagnosis, though it is not a formal criterion.
- Sore throat is an underused Indian exam clue: a young adult with daily fever and severe persistent sore throat with a normal throat swab should prompt AOSD.
- Macrophage activation syndrome is the feared complication: rapidly falling platelets and fibrinogen, rising ferritin, transaminitis and splenomegaly demand urgent treatment.
- Atypical pericarditis, pleurisy and abdominal pain from serositis are recognised; chronic arthritis, particularly of wrists, develops in a subset.
A worked diagnostic pathway
A 32-year-old man has had daily fever to 39.5°C for three weeks with drenching sweats, a fleeting pink rash on his trunk, severe sore throat, wrist and knee pain, and 4 kg of weight loss. Blood count shows leucocytes of 17,000 with 88 per cent neutrophils; ESR and CRP are high.
Step one: mimic-check. Blood cultures, malaria and dengue serology, Widal test, urine culture, chest radiograph, echocardiography if endocarditis is plausible, and tuberculosis screening including IGRA are mandatory in India, because enteric fever, tuberculosis and brucellosis all masquerade as AOSD. Add HIV and hepatitis serology.
Step two: malignancy check. A lymphoma screen with examination for lymphadenopathy, lactate dehydrogenase and a CT scan of chest and abdomen, plus a peripheral smear, because lymphoma is the classic differential for fever with adenopathy and rash.
Step three: rheumatology screen. Rheumatoid factor and ANA are negative in AOSD by criteria; complement is normal or high. Ferritin is 9,800 ng/mL with glycosylated fraction of 12 per cent, and liver enzymes are mildly deranged.
Step four: apply Yamaguchi. Fever over a week, arthralgia over two weeks, typical rash and neutrophil leucocytosis give four major criteria; sore throat and abnormal liver enzymes add two minor. Six criteria, four major, with exclusions satisfied, classify AOSD.
Step five: treat in tiers. NSAIDs with gastroprotection plus a medium dose of prednisolone (0.5 to 1 mg per kg) control most disease, tapering slowly over months. Methotrexate is the standard steroid-sparing agent. Refractory or macrophage activation-prone disease responds best to IL-1 receptor blockade with anakinra; tocilizumab and canakinumab are alternatives. Monitor ferritin and CRP as treatment response markers.
Where the exam tries to catch you
Examiners rely on the fact that AOSD is a diagnosis of exclusion with a positive smear of mimics. The recurring stem is a young adult with quotidian fever, rash and leucocytosis where the wrong option is systemic lupus (ANA positive, leucopenia typical) or septicemia (positive cultures, different rash). Remember the arithmetic of the criteria: five criteria are needed and at least two must be major, so leucocytosis with fever alone cannot classify the disease. A second favourite is the ferritin trap, since ferritin is an acute-phase reactant and modest rises occur in any inflammation; it is the magnitude, in the thousands, plus a low glycosylated fraction that points to AOSD or haemophagocytic syndrome rather than ordinary infection.
Frequently asked questions
Which criteria set is used to diagnose AOSD?
The Yamaguchi criteria, which first require exclusion of infections, malignancy and other rheumatic diseases.
What is the pattern of the Still fever?
One spike per day to 39°C or more, typically in the evening, returning to normal between spikes, hence quotidian.
How does glycosylated ferritin help?
In AOSD the glycosylated fraction falls to 20 per cent or less of total ferritin, whereas in plain inflammation it stays above about 50 per cent.
Which biologic is usually first choice in refractory AOSD?
Anakinra, the interleukin-1 receptor antagonist, with rapid defervescence; tocilizumab and canakinumab are alternatives.
What is macrophage activation syndrome?
A life-threatening cytokine storm complicating AOSD, with pancytopenia, very high ferritin, low fibrinogen and transaminitis, treated urgently with steroids and anakinra.