What are the diagnostic criteria and treatment options for Adult-Onset Still's Disease (AOSD)?

Diagnosing Adult-Onset Still's Disease (AOSD)

Adult-Onset Still's Disease should be diagnosed using the Yamaguchi criteria, which requires ≥5 criteria with at least 2 major criteria, including fever ≥39°C for ≥1 week, arthralgia ≥2 weeks, typical rash, and leukocytosis with neutrophilia. 1

Key Diagnostic Features

Major Clinical Manifestations

• Fever: Typically spiking with temperature ≥39°C (102.2°F) for at least 7 days, often with quotidian or double-quotidian pattern 2
• Rash: Transient, salmon-pink, maculopapular, often coinciding with fever spikes, preferentially involving the trunk 2
• Musculoskeletal involvement:
  • Arthralgia/myalgia is usually present
  • Arthritis may appear later (median delay of 1 month after disease onset) 2
  • Common joints affected: knees (82%), wrists (73%), ankles (55%), proximal interphalangeal joints (47%) 2
• Laboratory markers of inflammation:
  • Neutrophilic leukocytosis (often >15,000/mm³ with >80% neutrophils)
  • Elevated ESR and CRP
  • Markedly elevated serum ferritin (4,000-30,000 ng/mL, sometimes as high as 250,000 ng/mL) 2, 1

Minor Criteria

• Sore throat (38-92% of patients) 2
• Lymphadenopathy and/or splenomegaly (32-74% of patients) 2
• Liver dysfunction (50-75% of patients) 2
• Negative rheumatoid factor (RF) and antinuclear antibody (ANA) tests 1

Diagnostic Algorithm

1. Initial evaluation:

   • Document pattern of fever (daily temperature chart)
   • Characterize rash (photograph if possible)
   • Document joint symptoms (arthralgia vs. arthritis)
   • Order laboratory tests:
     • Complete blood count with differential
     • ESR and CRP
     • Serum ferritin
     • Liver function tests
     • RF and ANA
     • Glycosylated ferritin (if available; <20% is highly specific for AOSD) 1

2. Apply Yamaguchi criteria:

   • Major criteria: fever ≥39°C for ≥1 week, arthralgia ≥2 weeks, typical rash, leukocytosis
   • Minor criteria: sore throat, lymphadenopathy/splenomegaly, liver dysfunction, negative RF and ANA
   • Diagnosis requires ≥5 criteria with at least 2 major criteria 3

3. Rule out differential diagnoses:

   • Infectious diseases (viral syndromes, bacterial infections)
   • Malignancies (leukemia, lymphoma)
   • Autoimmune disorders (SLE, vasculitis)
   • Other inflammatory conditions 2

4. Additional diagnostic markers (if available):

   • Serum IL-18 (markedly elevated levels strongly support diagnosis) 2
   • S100 proteins (e.g., calprotectin) 2

Diagnostic Pitfalls and Caveats

1. Delayed diagnosis is common due to:

   • Heterogeneous presentation
   • Lack of specific diagnostic tests
   • Need to exclude other conditions 4

2. Arthritis may appear later in the disease course:

   • Do not delay diagnosis waiting for arthritis to develop
   • Arthralgia is sufficient for diagnosis 2

3. Potential complications requiring vigilance:

   • Macrophage activation syndrome (MAS): persistent fever, cytopenias, rising ferritin, liver dysfunction 1
   • Acute liver failure (rare but potentially fatal) 5
   • Cardiac involvement (pericarditis in 23-37% of patients) 2
   • Still's lung disease: screen with pulmonary function tests and high-resolution CT for symptomatic patients 1

4. Disease patterns to recognize:

   • Monocyclic (single episode with resolution): 30%
   • Polycyclic/intermittent (recurrent episodes): 30%
   • Chronic articular (persistent arthritis): 40% 1

Treatment Approach

Once diagnosed, treatment should follow a stepwise approach:

1. First-line therapy: NSAIDs (effective as monotherapy in only 7-15% of patients)
2. Second-line therapy: Corticosteroids (prednisone 0.5-1 mg/kg/day)
3. Third-line therapy:
   • Conventional DMARDs (methotrexate)
   • Biological agents: IL-1 inhibitors (anakinra, canakinumab) or IL-6 inhibitors (tocilizumab) 1

The 2024 EULAR/PReS recommendations suggest initiating IL-1 or IL-6 inhibitors as early as possible when diagnosis is established, with the goal of achieving clinically inactive disease (absence of symptoms and normal inflammatory markers) 2.