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

Diagnostic Criteria for Systemic Lupus Erythematosus

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

Mandatory Entry Criterion: ANA Testing

• ANA positivity at titer ≥1:80 by indirect immunofluorescence on HEp-2 cells is absolutely required - without this, SLE classification cannot proceed regardless of other clinical manifestations 1, 3
• If ANA is negative at ≥1:80, SLE is effectively ruled out in most cases 3
• For unselected populations, use 1:160 dilution as the cut-off point to improve specificity from 74.7% to 86.2% while maintaining 95.8% sensitivity 1, 3, 4

Critical Caveat About ANA Specificity

• At the standard 1:80 titer, specificity is only 74.7%, meaning approximately 1 in 4 positive results may be false positives for SLE 1, 4
• ANA positivity occurs in 13.3% of healthy individuals at 1:80 dilution and 5.0% at 1:160 dilution 1, 4
• Never rely on ANA alone - positive ANA requires confirmation with specific autoantibodies and clinical correlation 1

Weighted Scoring System (Requires ≥10 Points)

After confirming positive ANA, evaluate the following domains with their assigned point values 1:

Constitutional Domain

• Fever >38.3°C (unexplained) 1

Hematologic Domain

• Leukopenia, thrombocytopenia, or autoimmune hemolysis 1

Neuropsychiatric Domain

• Delirium, psychosis, or seizures (after excluding other causes) 1

Mucocutaneous Domain

• Acute or subacute cutaneous lupus, oral ulcers, alopecia, or discoid lesions 1

Musculoskeletal Domain

• Arthritis involving ≥2 joints 1

Serosal Domain

• Pleural or pericardial effusion, or acute pericarditis 1

Renal Domain

• Proteinuria >0.5g/24h or red blood cell casts 1
• 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 Markers)

• Anti-dsDNA antibodies - highly specific for SLE 1, 5
• Anti-Smith (Sm) antibodies - highly specific for SLE 5
• Antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, or anti-β2-glycoprotein I) 1
• Low complement (C3, C4) - indicates active disease 1
• Anti-Ro/SSA, anti-La/SSB, anti-RNP antibodies 1

Diagnostic Algorithm in Clinical Practice

Step 1: Initial Screening

• Screen with ANA testing when clinical suspicion exists based on rash, arthritis, serositis, unexplained cytopenias, or renal dysfunction 1

Step 2: Confirmatory Testing (If ANA ≥1:80 Positive)

• Order specific autoantibody panel including anti-dsDNA, anti-Sm, anti-Ro/SSA, anti-La/SSB, antiphospholipid antibodies 1, 3
• For anti-dsDNA testing, use double-screening strategy with solid-phase assay (SPA) such as FEIA and Crithidia luciliae immunofluorescence test (CLIFT) 3
• Interpretation hierarchy: SPA positive + CLIFT positive indicates SLE is very likely; SPA negative + CLIFT negative indicates SLE diagnosis cannot be established at this time 3

Step 3: Assess Disease Activity and Organ Involvement

• Measure complement levels (C3, C4) 1, 3
• Complete blood count for cytopenias 3
• Urinalysis with proteinuria quantification and urinary sediment examination 3
• Serum creatinine 3
• For suspected lupus nephritis, renal biopsy provides definitive diagnosis and prognostic information 3
• Anti-C1q antibodies are found in almost 100% of patients with active lupus nephritis 3

Step 4: Neuropsychiatric Evaluation (If Indicated)

• Perform brain MRI for neuropsychiatric symptoms 1, 3
• Exclude alternative diagnoses before attributing symptoms to SLE 1

Essential Pitfalls to Avoid

• 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
• 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 1
• Include detailed clinical information with laboratory requests to help laboratories assess results and determine appropriate follow-up testing 1, 4
• Do not repeat ANA testing for monitoring disease activity once diagnosis is established - instead, use quantitative anti-dsDNA assays with the same method consistently 4
• If clinical suspicion is high, test for specific antibodies regardless of ANA titer or even if ANA is negative 4