What are the diagnostic criteria for Systemic Lupus Erythematosus (SLE)?

Diagnostic Criteria for Systemic Lupus Erythematosus

The EULAR/ACR 2019 classification criteria are the current standard for diagnosing SLE, requiring positive ANA (≥1:80 titer) as an absolute entry criterion, followed by weighted scoring of clinical and immunological features to reach a threshold of ≥10 points, achieving 96.1% sensitivity and 93.4% specificity. 1, 2

Entry Criterion: Antinuclear Antibodies (ANA)

ANA positivity at titer ≥1:80 by indirect immunofluorescence on HEp-2 cells is mandatory - without this, SLE classification cannot proceed regardless of other manifestations. 3, 1, 4

Critical Caveats About ANA Testing:

• At 1:80 titer, specificity is only 74.7%, meaning approximately 1 in 4 positive results may be false positives for SLE 3, 5
• At 1:160 titer, specificity improves to 86.2% while maintaining 95.8% sensitivity, providing better diagnostic performance 3, 5, 4
• ANA positivity occurs in 13.3% of healthy individuals at 1:80 dilution and 5.0% at 1:160 dilution 5

Weighted Clinical and Immunological Domains

After confirming positive ANA, evaluate the following domains with their point values to reach ≥10 points for SLE classification 1, 2:

Constitutional Domain:

• Fever (unexplained, >38.3°C) 1

Hematologic Domain:

• Leukopenia, thrombocytopenia, or autoimmune hemolysis 3, 2

Neuropsychiatric Domain:

• Delirium, psychosis, or seizures (after excluding other causes) 3

Mucocutaneous Domain:

• Acute or subacute cutaneous lupus, oral ulcers, alopecia, or discoid lesions 3

Musculoskeletal Domain:

• Arthritis involving ≥2 joints 3

Serosal Domain:

• Pleural or pericardial effusion, or acute pericarditis 3

Renal Domain:

• Proteinuria >0.5g/24h or red blood cell casts - lupus nephritis develops in 40% of SLE patients and progresses to end-stage renal disease in 10% at 10 years 1, 2

Immunologic Domain (High Specificity):

• Anti-dsDNA antibodies - highly specific for SLE 3
• Anti-Smith (Sm) antibodies - highly specific confirmatory test 6
• Antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, or anti-β2-glycoprotein I) 3
• Low complement (C3, C4) - indicates active disease 3
• Anti-Ro/SSA, anti-La/SSB, anti-RNP antibodies 3

Diagnostic Algorithm in Practice

1. Screen with ANA testing when clinical suspicion exists (rash, arthritis, serositis, unexplained cytopenias, renal dysfunction) 3, 4

2. If ANA ≥1:80 positive, order specific autoantibody panel including anti-dsDNA, anti-Sm, anti-Ro/SSA, anti-La/SSB, antiphospholipid antibodies 3, 5

3. Assess complement levels (C3, C4) and complete blood count 3

4. Evaluate for organ involvement with urinalysis (proteinuria, hematuria, casts), serum creatinine, and consider renal biopsy if nephritis suspected 3, 2

5. For neuropsychiatric symptoms, perform brain MRI and exclude alternative diagnoses before attributing to SLE 3

Essential Pitfalls to Avoid

Do not rely on ANA alone - the low specificity (74.7% at 1:80) means positive ANA requires confirmation with specific autoantibodies and clinical correlation 3, 5

Classification criteria are not formal diagnostic criteria - they were developed for research purposes, though widely used clinically. SLE remains fundamentally a clinical diagnosis after excluding alternatives 1, 7, 8

For intermediate ANA titers (1:80-1:160), consider testing anti-Ro antibodies as the Ro ribonucleoprotein is clinically important in SLE and related conditions 3

Include detailed clinical information with laboratory requests to help laboratories assess results and determine appropriate follow-up testing 3