What laboratory tests are necessary to differentiate between Adult-Onset Still's Disease (AOSD), vasculitis, and eczema?

Laboratory Tests to Differentiate Adult-Onset Still's Disease (AOSD), Vasculitis, and Eczema

The most essential laboratory tests to differentiate between Adult-Onset Still's Disease (AOSD), vasculitis, and eczema include complete blood count with differential, inflammatory markers (ESR, CRP), ferritin with glycosylated fraction, autoantibody testing (ANA, RF), and specific biomarkers like IL-18 and S100 proteins. 1

Core Laboratory Tests for All Three Conditions

• Complete blood count (CBC) with differential - AOSD typically shows marked neutrophilic leukocytosis, while vasculitis may show variable patterns and eczema typically has normal counts or mild eosinophilia 1
• Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) - Both are significantly elevated in AOSD and vasculitis, but typically normal or mildly elevated in eczema 1
• Liver function tests (LFTs) - Abnormal in 50-75% of AOSD patients, may be normal or mildly elevated in vasculitis, and typically normal in eczema 1
• Antinuclear antibody (ANA) and rheumatoid factor (RF) - Both are negative in AOSD (important diagnostic criterion), may be positive in some vasculitides, and typically negative in eczema 1, 2

Specific Tests for AOSD

• Serum ferritin - Very high levels (4,000-30,000 ng/ml or even up to 250,000 ng/ml) strongly suggest AOSD 1
• Glycosylated ferritin fraction - Less than 20% is highly specific for AOSD (normally 50-80% in healthy subjects) 1
• Interleukin-18 (IL-18) - Marked elevation strongly supports AOSD diagnosis 1
• S100 proteins (calprotectin) - Significantly elevated in AOSD 1
• Neutrophil-to-lymphocyte ratio (NLR) - A cutoff value of 3.08 has shown 91.7% sensitivity and 68.4% specificity for AOSD diagnosis 3
• Systemic immune-inflammation index (SII) combined with ferritin - Has shown excellent diagnostic accuracy for AOSD (AUC = 0.904) 4

Specific Tests for Vasculitis

• Antineutrophil cytoplasmic antibodies (ANCA) - Anti-PR3 (c-ANCA) and anti-MPO (p-ANCA) are highly specific for small-vessel vasculitides 2
• Complement levels (C3, C4) - May be decreased in some forms of vasculitis 2
• Cryoglobulins - Important for diagnosing cryoglobulinemic vasculitis 2
• Urinalysis - To detect renal involvement, which significantly impacts prognosis in vasculitis 2

Differential Diagnostic Approach

For AOSD Diagnosis:

1. First-line tests:

   • CBC with differential (looking for neutrophilic leukocytosis)
   • ESR and CRP (markedly elevated)
   • Ferritin (very high levels >5x normal)
   • LFTs (often abnormal)
   • ANA and RF (both negative) 1

2. Second-line tests:

   • Glycosylated ferritin fraction (if available)
   • IL-18 and S100 proteins (if available)
   • NLR calculation from CBC 1, 3

For Vasculitis Diagnosis:

1. First-line tests:

   • CBC with differential
   • ESR and CRP
   • ANCA testing (c-ANCA and p-ANCA)
   • Urinalysis
   • Renal function tests 2

2. Second-line tests:

   • Complement levels
   • Cryoglobulins
   • Tissue biopsy (often required for definitive diagnosis) 2

For Eczema Diagnosis:

• Laboratory tests are typically normal in eczema, which is primarily diagnosed clinically
• Mild eosinophilia may be present in some cases
• IgE levels may be elevated in atopic eczema

Important Considerations

• AOSD is now considered the same disease as systemic juvenile idiopathic arthritis (sJIA), collectively referred to as "Still's disease" 1
• The combination of very high ferritin (>5x normal) with a glycosylated ferritin fraction <20% has 43% sensitivity but 93% specificity for AOSD 1
• Alternative diagnoses such as malignancies, infectious diseases, and monogenic autoinflammatory disorders must be carefully considered and excluded before diagnosing AOSD 1
• Macrophage activation syndrome (MAS) is a life-threatening complication of AOSD that requires specific laboratory monitoring (persistent fever, rising ferritin, falling cell counts, abnormal LFTs, elevated triglycerides) 1, 5

By systematically applying these laboratory tests and considering the clinical presentation, clinicians can effectively differentiate between AOSD, vasculitis, and eczema, leading to appropriate management strategies and improved patient outcomes.