What labs should be ordered for the differential diagnosis of Adult-Onset Still's Disease (AOSD), eczema, and vasculitis?

Laboratory Tests for Differential Diagnosis of Adult-Onset Still's Disease (AOSD), Eczema, and Vasculitis

For accurate differential diagnosis of Adult-Onset Still's Disease (AOSD), eczema, and vasculitis, a comprehensive laboratory panel including ferritin, glycosylated ferritin, and specific inflammatory markers is essential to guide appropriate treatment decisions.

Core Laboratory Tests

• Complete Blood Count (CBC) with differential - Essential for detecting neutrophilia (common in AOSD), eosinophilia (may suggest eczema), or cytopenias (may occur in vasculitis) 1, 2
• Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP) - Elevated in all three conditions but particularly high in AOSD and vasculitis 1, 3
• Ferritin levels - Extremely high levels (>1000 ng/mL) strongly suggest AOSD with sensitivity of 74.5-96.7% and specificity of 50-94.1% depending on the cutoff used 1
• Glycosylated ferritin (GF) - GF ≤20% has 79.5% sensitivity and 66.4% specificity for AOSD; combined with elevated ferritin improves diagnostic accuracy 1
• Liver function tests - Abnormal in 76.6% of AOSD patients 2
• Rheumatoid factor (RF) and antinuclear antibodies (ANA) - Typically negative in AOSD (important for differentiation from other rheumatic diseases) 2

AOSD-Specific Biomarkers

• Interleukin-18 (IL-18) - Markedly elevated in AOSD with high sensitivity (80-95%) and specificity (93-100%) depending on cutoff values 1
• S100A8/A9 protein (calprotectin) - Elevated in AOSD with sensitivity of 63-69.4% and specificity of 80.1-98% 1
• S100A12 protein - Can help differentiate AOSD from other inflammatory conditions 1

Vasculitis-Specific Tests

• Anti-neutrophil cytoplasmic antibodies (ANCA) - Essential for diagnosing ANCA-associated vasculitis; high-quality antigen-specific immunoassays are preferred 3
• Anti-glomerular basement membrane (GBM) antibodies - Important for anti-GBM antibody disease 3
• Complement levels (C3, C4) - To distinguish normocomplementaemic from hypocomplementaemic urticarial vasculitis 4
• Cryoglobulins - For suspected cryoglobulinemic vasculitis 3
• Hepatitis B and C serology - Important for vasculitis associated with viral infections 3
• Immunoglobulin levels - May be elevated in certain forms of vasculitis 3

Eczema-Related Tests

• Serum IgE levels - Often elevated in atopic eczema 4
• Thyroid function tests - Recommended if chronic urticaria is suspected as part of the differential 4

Additional Important Tests

• Skin biopsy - Essential for histopathological examination to distinguish between AOSD, vasculitis, and eczema 4, 5
• Cultures and serological tests - To exclude infectious causes that can mimic these conditions 1
• Anti-cyclic citrullinated peptide (CCP) antibody - To rule out rheumatoid arthritis, though can occasionally be positive in AOSD with arthritis 6

Diagnostic Algorithm

1. Initial screening panel: CBC, ESR, CRP, ferritin, liver function tests, RF, ANA 1
2. If ferritin >1000 ng/mL: Order glycosylated ferritin, IL-18, and S100 proteins to confirm AOSD 1
3. If vasculitis is suspected: Order ANCA, anti-GBM antibodies, complement levels, cryoglobulins, and viral serology 3
4. If eczema is suspected: Order IgE levels and consider thyroid function tests 4
5. Consider skin biopsy in all cases for definitive diagnosis 4, 5

Common Pitfalls and Caveats

• Ferritin levels alone are not specific enough for AOSD diagnosis; glycosylated ferritin improves specificity 1
• Negative autoantibodies (RF, ANA) support AOSD diagnosis but do not rule out vasculitis 2
• Overlapping conditions can occur - AOSD can be complicated by IgA vasculitis as reported in case studies 6
• Atypical cutaneous manifestations of AOSD can mimic eczema or vasculitis, making skin biopsy crucial 5
• Fever of unknown origin with abdominal pain and mesenteric lymphadenopathy may lead to unnecessary exploratory procedures before AOSD is considered 1, 7

Special Considerations

• Macrophage activation syndrome (MAS) is a life-threatening complication of AOSD; monitor for cytopenias, elevated triglycerides, and hemophagocytosis 1
• Periodic fever syndromes (familial Mediterranean fever, TRAPS) can mimic AOSD and should be considered in the differential diagnosis 1
• Neoplastic disorders (leukemia, lymphoma) can present similarly to AOSD and should be ruled out, especially in older adults 1