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

SLE Diagnosis Criteria

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

Mandatory Entry Criterion

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 present. 1

Critical ANA Testing Caveats

• 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, 3
• Consider using 1:160 titer as a more reliable cutoff, which improves specificity to 86.2% while maintaining 95.8% sensitivity. 1, 3
• ANA positivity occurs in 13.3% of healthy individuals at 1:80 dilution and 5.0% at 1:160 dilution, limiting diagnostic utility at lower titers. 3

Weighted Scoring System (Need ≥10 Points)

After confirming positive ANA, evaluate the following clinical and immunological domains with their assigned point values to reach the ≥10 point threshold for SLE classification. 1

Constitutional Domain

• Fever (unexplained, >38.3°C). 1

Hematologic Domain

• Leukopenia, thrombocytopenia, or autoimmune hemolysis. 1

Neuropsychiatric Domain

• Delirium, psychosis, or seizures (after excluding alternative causes such as infection, metabolic derangement, or medication effects). 1

Mucocutaneous Domain

• Acute or subacute cutaneous lupus, oral ulcers (typically painless), non-scarring alopecia, or discoid lesions. 1

Musculoskeletal Domain

• Arthritis involving ≥2 joints with tenderness and swelling. 1

Serosal Domain

• Pleural or pericardial effusion, or acute pericarditis. 1

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, making early detection critical for mortality reduction. 1, 2

Immunologic Domain (High Specificity Markers)

• Anti-dsDNA antibodies - highly specific for SLE and included as classification criteria. 4, 1
• Antiphospholipid antibodies (lupus anticoagulant, anticardiolipin IgG/IgM, or anti-β2-glycoprotein I). 1
• Low complement (C3, C4) - indicates active disease with immune complex consumption. 1
• Anti-Sm antibodies (highly specific but less sensitive). 1
• Anti-Ro/SSA, anti-La/SSB, anti-RNP antibodies. 1

Diagnostic Algorithm in Clinical Practice

Step 1: Screen with ANA when clinical suspicion exists based on unexplained rash (particularly malar or photosensitive), inflammatory arthritis, serositis, unexplained cytopenias, or renal dysfunction with proteinuria/hematuria. 1

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

Step 3: Assess complement levels (C3, C4) and complete blood count to evaluate for active immune complex-mediated disease and cytopenias. 1

Step 4: Evaluate for organ involvement with urinalysis (proteinuria, hematuria, cellular casts), serum creatinine, and strongly consider renal biopsy if nephritis suspected to guide aggressive immunosuppression. 1

Step 5: For neuropsychiatric symptoms, perform brain MRI and rigorously exclude infection, metabolic causes, and medication effects before attributing symptoms to SLE. 1

Essential Pitfalls to Avoid

• Never rely on ANA alone for diagnosis - the poor specificity (74.7% at 1:80) means positive ANA requires confirmation with specific autoantibodies and clinical correlation to avoid misdiagnosis. 1, 3

• Recognize that classification criteria are not formal diagnostic criteria - they were developed for research homogeneity in clinical trials, though widely adopted clinically. SLE remains fundamentally a clinical diagnosis after excluding mimics. 4, 5

• For intermediate ANA titers (1:80-1:160), test anti-Ro antibodies as the Ro ribonucleoprotein is clinically important in SLE and related conditions, and may be missed with standard panels. 3

• Provide detailed clinical information with laboratory requests to help laboratories assess results appropriately and determine whether reflex testing for specific antibodies is warranted. 1

• Do not delay treatment while awaiting classification criteria fulfillment - patients with life-threatening manifestations (severe nephritis, neuropsychiatric disease, cytopenias) require immediate immunosuppression even if they do not yet meet full criteria. 2, 6