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

Diagnostic Criteria for Systemic Lupus Erythematosus (SLE)

The 2019 EULAR/ACR classification criteria are the current gold standard for diagnosing SLE, requiring positive antinuclear antibodies (ANA) as an absolute entry criterion, followed by a weighted scoring system of clinical and immunological domains, achieving 96.1% sensitivity and 93.4% specificity. 1, 2, 3

Entry Criterion (Mandatory)

• Positive ANA testing is absolutely required to proceed with SLE classification—without positive ANA, a patient cannot be classified as SLE regardless of other manifestations 2
• ANA positivity must be demonstrated at least once by immunofluorescence on HEp-2 cells or equivalent assay 1

Weighted Clinical and Immunological Domains

After confirming positive ANA, the EULAR/ACR 2019 criteria use a point-based system across multiple domains 1, 3:

Constitutional Domain

• Fever (temperature >38.3°C after excluding infection) 3

Hematologic Domain

• Leukopenia (<4,000/mm³) 3
• Thrombocytopenia (<100,000/mm³) 3
• Autoimmune hemolysis 3

Neuropsychiatric Domain

• Delirium, psychosis, seizures 3

Mucocutaneous Domain

• Lupus-specific rash (acute cutaneous lupus, subacute cutaneous lupus, discoid lupus) 4, 3
• Oral ulcers (typically painless) 4
• Non-scarring alopecia 4

Serosal Domain

• Pleural or pericardial effusion 3

Musculoskeletal Domain

• Joint involvement (synovitis in ≥2 joints or tenderness in ≥2 joints with morning stiffness) 4, 3

Renal Domain

• Proteinuria (>0.5 g/24 hours or equivalent protein/creatinine ratio) 3
• Renal biopsy showing Class II or V lupus nephritis 3
• Renal biopsy showing Class III or IV lupus nephritis (carries highest weight) 3

Immunologic Domain

• Anti-dsDNA antibodies 1, 3
• Anti-Smith (anti-Sm) antibodies 3, 5
• Antiphospholipid antibodies (lupus anticoagulant, anti-cardiolipin IgG/IgM, or anti-β2-glycoprotein I IgG/IgM) 3
• Low complement levels (low C3 and/or low C4) 3, 5

Scoring and Classification

• Each domain carries a specific weighted score, with more specific manifestations (like Class III/IV lupus nephritis) carrying higher weights 1, 3
• A total score of ≥10 points classifies the patient as having SLE 1, 3
• The criteria were developed using both expert consensus and data-driven methods, demonstrating superior performance compared to all previous classification systems 1

Critical Distinctions and Pitfalls

• These are classification criteria, not formal diagnostic criteria, though they are widely used in clinical practice for diagnosis 2, 5
• The multifactorial nature of SLE generates numerous phenotypes without a single common etiology—manifestations can occur simultaneously or at different times in a patient's history 1
• Anti-dsDNA antibodies are heterogeneous and lack proper standardization across different assay methods, which can lead to inconsistent results 1
• Anti-dsDNA antibodies are found in several disorders besides SLE, and their diagnostic performance varies depending on the population studied 1
• Approximately 40% of SLE patients develop lupus nephritis, with 10% progressing to end-stage kidney disease within 10 years 2, 3

Laboratory Evaluation Beyond Classification

Regular monitoring should include 6:

• Complete blood count
• Serum creatinine and proteinuria assessment
• Urine sediment analysis
• Complement levels (C3, C4)
• Anti-dsDNA titers
• Additional autoantibodies (anti-Ro/SSA, anti-La/SSB, anti-RNP) as clinically indicated