What diagnostic tests are used to diagnose lupus?

Diagnostic Tests for Lupus

The essential diagnostic tests for lupus include antinuclear antibody (ANA) testing as the primary screening test, followed by specific autoantibody tests including anti-dsDNA, anti-Ro, anti-La, anti-RNP, anti-Sm, anti-phospholipid antibodies, and complement levels (C3, C4). 1

Initial Laboratory Evaluation

First-line Testing

• Antinuclear antibody (ANA) by indirect immunofluorescence on HEp-2 cells
  • Primary screening test with high sensitivity
  • A negative ANA test makes SLE diagnosis unlikely 2
  • Should only be obtained in patients with unexplained involvement of two or more organ systems

Second-line Testing (if ANA positive or strong clinical suspicion)

• Anti-dsDNA antibodies
  • Highly specific for SLE
  • Associated with renal involvement
  • Methods: Farr assay (most accurate), CLIFT (Crithidia Luciliae Immunofluorescence Test), or ELISA 3
• Anti-Sm (Smith) antibodies
  • Highly specific for SLE
  • Strong confirmatory value even when pre-test probability is low 4
• Complement levels (C3, C4)
  • Low levels suggest active disease
• Anti-Ro and Anti-La antibodies
  • Important to check before pregnancy
• Anti-RNP antibodies
• Anti-phospholipid antibodies
  • Important before pregnancy, surgery, transplant, or when using estrogen-containing treatments 1

Additional Laboratory Tests

• Complete blood count
• Erythrocyte sedimentation rate (ESR)
• C-reactive protein (CRP)
• Serum albumin
• Serum creatinine (or eGFR)
• Urinalysis and urine protein/creatinine ratio 1

Organ-Specific Evaluation

Renal Assessment

• Urine protein/creatinine ratio (or 24-hour proteinuria)
• Urine microscopy
• Renal ultrasound
• Kidney biopsy (if persistent abnormal urinalysis or elevated creatinine) 1, 5

Neuropsychiatric Assessment

• Focused neurological history for symptoms like seizures, paresthesias, numbness, weakness, headache
• Cognitive assessment (attention, concentration, memory difficulties) 1

Mucocutaneous Assessment

• Characterization of skin lesions as:
  • LE specific
  • LE non-specific
  • LE mimickers
  • Drug-related 1

Monitoring Tests

Disease Activity Monitoring (every 1-3 months)

• Anti-dsDNA antibodies
• Complement levels (C3, C4)
• Complete blood count
• Renal function tests
• Urinalysis and proteinuria 5

For Patients with Inactive Disease (every 6-12 months)

• Complete blood count
• ESR
• CRP
• Serum albumin
• Serum creatinine
• Urinalysis and urine protein/creatinine ratio 1

Special Considerations

• Lupus anticoagulant testing requires specific protocols:

  • Two tests based on different principles (dRVVT as first choice)
  • Proper blood collection and processing (double centrifugation)
  • Mixing studies and confirmatory tests with increased phospholipid concentration 1

• Anti-phospholipid antibody testing is crucial before:

  • Pregnancy
  • Surgery
  • Transplantation
  • Starting estrogen-containing treatments
  • When new neurological or vascular events occur 1, 5

Common Pitfalls to Avoid

1. Overreliance on single tests: No single test can diagnose lupus; a combination of clinical and laboratory criteria is needed

2. Testing without clinical context: ANA testing should only be performed in patients with unexplained involvement of multiple organ systems 2

3. Misinterpreting ANA titers: Low titers (1:40) have poor specificity and may require additional testing 2

4. Inadequate follow-up testing: Patients with persistent symptoms but negative initial tests may need repeated or expanded testing

5. Poor sample handling: Improper collection or processing can affect test results, particularly for lupus anticoagulant testing 1

6. Discontinuing monitoring too early: Regular monitoring should continue even during remission, as disease flares can occur despite prolonged immunosuppression 5