How can I confirm a diagnosis of systemic lupus erythematosus in a patient?

How to Confirm a Diagnosis of Systemic Lupus Erythematosus

Start with ANA testing by indirect immunofluorescence on HEp-2 cells at a screening dilution of 1:80-1:160, as this provides >95% sensitivity and effectively rules out SLE when negative. 1

Initial Screening Approach

ANA is your gatekeeper test - a negative ANA by immunofluorescence makes SLE highly unlikely (negative predictive value >95%) and should prompt you to consider alternative diagnoses. 1 However, a critical pitfall: never use automated ANA platforms (ELISA, multiplex) as your sole screening test - they have lower sensitivity and may miss relevant antibodies. 1 If you must use an automated platform, document the specific method clearly and don't simply label it as "ANA test." 1

• Report both the ANA titer AND the immunofluorescence pattern; titers ≥1:160 are clinically significant, and a homogeneous pattern associates with more severe disease activity. 1
• Only order ANA when the patient has unexplained involvement of two or more organ systems - the low prevalence of SLE in primary care makes ANA testing have poor predictive value without typical clinical symptoms. 2

Comprehensive Autoantibody Panel (When ANA is Positive)

Once ANA is positive at ≥1:160, immediately order a complete autoantibody panel including anti-dsDNA, anti-Sm, anti-Ro/SSA, anti-La/SSB, anti-RNP, antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, anti-β2-glycoprotein I), and complement levels (C3, C4). 3, 1

Anti-dsDNA Testing Strategy (Critical for Specificity)

Use a double-screening approach for anti-dsDNA: first perform a solid-phase assay (ELISA/FEIA) for high sensitivity, then confirm all positives with Crithidia luciliae immunofluorescence test (CLIFT) for higher specificity. 1

• Both positive (SPA + CLIFT): Very high likelihood of SLE - proceed with full organ assessment. 1
• SPA positive but CLIFT negative: Interpret cautiously in clinical context and repeat anti-dsDNA in approximately 6 months. 1
• Special circumstance: If ANA is negative but you strongly suspect lupus nephritis based on clinical features, you may still order anti-dsDNA testing. 1

High-Specificity Antibodies

Anti-dsDNA and anti-Sm antibodies are highly specific for SLE - their presence strongly supports the diagnosis. 1, 2

Essential Baseline Laboratory Assessment

Obtain these tests in all patients with suspected SLE:

• Complete blood count with differential - screens for cytopenias; severe lymphopenia (<500 cells/mm³) or neutropenia (<500 cells/mm³) signals high infection risk. 1
• ESR and CRP - baseline inflammatory markers. 1
• Serum creatinine or eGFR - assess renal function. 1
• Urinalysis with microscopy PLUS urine protein/creatinine ratio - essential to detect renal involvement. 1
• Serum albumin - identifies hypoalbuminemia from disease activity or renal loss. 1
• Liver function tests - part of baseline metabolic panel. 1

Organ-Specific Clinical Assessment

Renal Evaluation (High Priority for Morbidity/Mortality)

For any patient with persistently abnormal urinalysis or rising serum creatinine, immediately order: repeat urine protein/creatinine ratio (or 24-hour proteinuria), urine microscopy, renal ultrasound, and strongly consider renal biopsy (Level 1b evidence, Grade B recommendation). 3, 1

• Renal biopsy is advised when there is uncertainty about the nature or severity of renal involvement - this directly impacts treatment decisions and prognosis. 1

Mucocutaneous Assessment

Document all skin findings and classify them as:

• LE-specific (malar rash, discoid lesions, subacute cutaneous lupus)
• LE-nonspecific
• LE mimickers
• Drug-related 3, 1

Use the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) for standardized documentation. 1

Neuropsychiatric Evaluation

Specifically query for: seizures, headaches, stroke-like symptoms, peripheral neuropathy, cognitive dysfunction (memory, attention, multitasking difficulties), and mood disorders (depression). 3, 1

• If cognitive impairment is suspected, assess attention, concentration, word finding, and memory difficulties by asking about problems with multitasking or household tasks. 3
• Perform a focused neurologic examination when symptoms are present. 1

Infection Screening Before Treatment

Before initiating high-dose glucocorticoids or immunosuppression, screen for:

• HIV, hepatitis C, and hepatitis B (based on individual risk factors) 1
• Tuberculosis according to local guidelines (typically interferon-γ release assay or tuberculin skin test with chest radiography) 1

Meeting Diagnostic/Classification Criteria

The SLICC 2012 criteria require: at least 4 criteria including at least one clinical criterion AND one immunologic criterion, OR biopsy-proven lupus nephritis in the presence of ANA or anti-dsDNA antibodies. 4

The SLICC criteria have greater sensitivity (94-97%) compared to older ACR criteria (83-86%) but slightly lower specificity (84-92%). 5, 4

Critical Pitfalls to Avoid

• Never repeat ANA testing after an initial positive result - it provides no clinical benefit for monitoring disease activity and is not cost-effective. 1
• Don't rely solely on ANA without further specific antibody testing - this leads to misdiagnosis. 1
• Rare ANA-negative SLE exists: If ANA is negative at 1:160 but the patient has multisystem involvement, consider ANA-negative SLE and repeat testing in 3-6 months. 1, 2
• Direct Coombs test is NOT a routine first-line test for SLE workup - only order it if peripheral blood smear shows spherocytes or schistocytes. 1

Monitoring After Diagnosis (Not Repeating ANA)

For disease activity monitoring, use:

• Serial C3 and C4 complement levels at every visit 1
• Quantitative anti-dsDNA antibody levels combined with complement concentrations 1
• Never use ANA titers for assessing disease activity 1