Introduction
Adult-Onset Still’s Disease (AOSD) is a rare systemic inflammatory disorder characterized by the classic triad of high spiking fevers, evanescent rash, and arthralgia or arthritis. Because it lacks pathognomonic serological markers, AOSD is a diagnosis of exclusion and a prominent non-infectious cause of Pyrexia of Unknown Origin (PUO).
Clinical Manifestations
The clinical presentation of AOSD can mimic severe sepsis, occult malignancy, or systemic vasculitis:
High Spiking Fever: Typically quotidian (once daily) or double-quotidian, exceeding $39.0^\circ\text{C}$, often spiking in the late afternoon or evening.
Evanescent Rash: Salmon-pink, maculopapular eruption that typically accompanies fever spikes and fades as temperature normalizes.
Musculoskeletal Symptoms: Arthralgia and inflammatory arthritis affecting knees, wrists, ankles, and elbows.
Other Features: Pharyngitis (sore throat), lymphadenopathy, hepatosplenomegaly, and polyserositis (pleuritis/pericarditis).
Diagnostic Framework: Yamaguchi Criteria
Yamaguchi criteria are the most sensitive diagnostic tool for AOSD. Diagnosis requires $\ge 5$ criteria, with at least 2 being major criteria.
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| YAMAGUCHI CRITERIA FOR AOSD |
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| MAJOR CRITERIA: |
| 1. Fever >= 39°C lasting >= 1 week |
| 2. Arthralgia or arthritis lasting >= 2 weeks |
| 3. Typical salmon-pink evanescent rash during fever |
| 4. Leukocytosis (WBC >= 10,000/mcL with >= 80% granulocytes) |
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| MINOR CRITERIA: |
| 1. Sore throat / Pharyngitis |
| 2. Lymphadenopathy and/or splenomegaly |
| 3. Abnormal liver function tests (AST, ALT, LDH) |
| 4. Negative ANA and Rheumatoid Factor (RF) |
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Laboratory Biomarkers & Management
Hyperferritinemia: Serum ferritin levels are markedly elevated (often $> 1,000\text{ ng/mL}$ and up to 5 times normal limits). Glycosylated ferritin fraction $< 20\%$ supports diagnosis.
Inflammatory Markers: Extreme elevation of ESR and CRP.
Therapeutic Approach:
First-line: High-dose Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) or systemic Corticosteroids (Prednisone 0.5–1 mg/kg/day).
Second-line (Refractory Cases): Disease-Modifying Antirheumatic Drugs (DMARDs) such as Methotrexate.
Biologic Therapy: IL-1 inhibitors (Anakinra, Canakinumab) or IL-6 inhibitors (Tocilizumab).