What laboratory tests should be ordered to diagnose lupus in a patient of unknown age, sex, and ethnicity with potential underlying medical conditions such as kidney disease or cardiovascular disease?

Laboratory Testing for Lupus Diagnosis

Start with an antinuclear antibody (ANA) test as your initial screening test, and if positive, proceed immediately with a comprehensive autoantibody panel including anti-dsDNA, anti-Sm, anti-Ro/SSA, anti-La/SSB, anti-RNP, antiphospholipid antibodies, complement levels (C3, C4), complete blood count, renal function tests, urinalysis with protein quantification, and inflammatory markers. 1, 2

Initial Screening Approach

• Order ANA first as it has extremely high sensitivity (nearly 100%) for ruling out SLE, making it the appropriate initial screening test 1, 3
• An ANA titer less than 1:40 essentially rules out lupus in most cases 3
• However, do not stop at ANA alone - relying solely on ANA without further specific antibody testing leads to misdiagnosis because ANA can be positive in many other conditions and even healthy individuals 1, 4

Comprehensive Autoantibody Panel (Order When ANA is Positive)

Highly Specific Antibodies for SLE

• Anti-dsDNA antibodies: Present in 40-80% of SLE patients and highly specific for the disease 2, 4
  • Use a double-screening strategy: solid-phase assay followed by Crithidia luciliae immunofluorescence test (CLIFT) for confirmation to maximize specificity 1, 2, 4
  • Avoid using ELISA alone in the diagnostic phase due to low specificity 4
• Anti-Sm antibodies: Highly specific for SLE and should always be included 1, 2, 5

Additional Autoantibodies with Clinical Significance

• Anti-Ro/SSA and anti-La/SSB antibodies: Critical to check at baseline, especially important before pregnancy due to risk of neonatal lupus and congenital heart block 1, 2
• Anti-RNP antibodies: Include as part of the comprehensive panel 1, 2
• Antiphospholipid antibodies: Essential to identify patients at risk for antiphospholipid syndrome 1, 2
  • Test for lupus anticoagulant and anti-cardiolipin antibodies using a beta2-glycoprotein I-dependent method 2, 4

Complement and Inflammatory Markers

• C3 and C4 complement levels: Required at baseline as they correlate with disease activity, particularly in lupus nephritis 1, 2
• Erythrocyte sedimentation rate (ESR): Helps distinguish inactive from active disease 1, 2
• C-reactive protein (CRP): Measure as part of inflammatory marker assessment 1, 2

Hematologic Assessment

• Complete blood count (CBC): Mandatory to detect cytopenias including anemia, leukopenia, and thrombocytopenia, which are common in SLE 1, 2

Renal Function Assessment

• Serum creatinine (or estimated glomerular filtration rate): Must be checked at baseline 1, 2
• Urinalysis: Essential to detect hematuria, pyuria, or casts 1, 2
• Urine protein/creatinine ratio: Obtain at baseline to assess for proteinuria 1, 2
• Serum albumin: Should be measured as part of baseline laboratory tests 1, 2

Additional Baseline Screening

Cardiovascular Risk Assessment

• Fasting lipid panel (cholesterol) and fasting glucose: Check at baseline and annually 6, 1, 2

Infection Screening

• HIV, hepatitis C virus, hepatitis B virus, and tuberculosis: Screen according to local guidelines at baseline 1, 2

Critical Pitfalls to Avoid

• Never order ANA in patients without multisystem involvement - the low prevalence of SLE in primary care means ANA has poor predictive value without characteristic clinical symptoms 3
• Do not diagnose lupus based on ANA alone - you need specific antibodies and clinical criteria 1
• Do not use ELISA for anti-dsDNA in the diagnostic phase - it has lower specificity than Farr assay or Crithidia luciliae immunofluorescence 4
• Remember that ANA-negative lupus exists - if a patient has persistent characteristic multisystem involvement despite negative ANA, further evaluation may still be warranted 3