What tests are used to diagnose lupus in a young to middle-aged woman, particularly those of African American, Hispanic, or Asian descent, presenting with symptoms such as joint pain, skin rashes, or kidney problems?

Laboratory Tests to Diagnose Systemic Lupus Erythematosus

Begin with ANA testing using a 1:160 dilution cutoff as the initial screening test, but only when clinical suspicion exists based on unexplained rashes, arthritis, serositis, neurological manifestations, or cytopenias—not for routine screening in asymptomatic patients. 1, 2

Initial Screening Strategy

• ANA testing serves as the entry criterion and should be performed using immunofluorescence with a 1:160 dilution cutoff to minimize false positives in unselected populations 2
• Only order ANA when clinical suspicion exists, such as unexplained disease involving two or more organ systems, to avoid false positives in low-prevalence populations 1, 3
• If ANA is negative but clinical suspicion remains high, proceed with anti-dsDNA testing and clinical follow-up, as some patients may have ANA-negative SLE 1

Confirmatory Autoantibody Panel (When ANA is Positive)

Once ANA is positive, immediately order a comprehensive autoantibody panel including anti-dsDNA, anti-Sm, anti-Ro/SSA, anti-La/SSB, anti-RNP, and antiphospholipid antibodies. 1, 2

Anti-dsDNA Antibodies

• Use a double-screening strategy: start with a solid-phase assay (FEIA, CLIA, or ELISA), then confirm with Crithidia luciliae immunofluorescence test (CLIFT) 1
• Anti-dsDNA correlates with disease activity and active renal disease, making it essential for both diagnosis and monitoring 2

Anti-ENA Panel

• Anti-Sm antibodies provide strong confirmatory evidence for SLE and offer prognostic value 1, 2
• Anti-Ro/SSA and anti-La/SSB must be checked at baseline due to their association with neonatal lupus risk—critical before pregnancy 4, 2
• Anti-RNP antibodies offer prognostic information for major organ involvement 4, 2

Antiphospholipid Antibodies

• Test for lupus anticoagulant, anticardiolipin, and anti-β2-glycoprotein I antibodies at baseline 4, 2
• These antibodies associate with thrombotic events, damage development, and pregnancy complications 4, 2
• For lupus anticoagulant detection, use two parallel tests: dilute Russell's viper venom time (dRVVT) and LA-sensitive activated partial thromboplastin time (APTT) 4
• Repeat positive antiphospholipid antibody testing after >12 weeks to confirm persistence 4

Complement Levels

• Measure C3 and C4 at baseline in all suspected SLE cases 4, 1, 2
• Low complement levels correlate with disease activity, predict flares, and indicate major organ involvement, especially renal disease 4, 2
• Low complement combined with positive anti-dsDNA strongly supports active SLE 2

Routine Hematologic and Chemistry Tests

Complete Blood Count

• CBC is mandatory at baseline to detect cytopenias (anemia, leukopenia, lymphopenia, thrombocytopenia) 4, 1, 2
• Severe anemia associates with organ involvement, disease progression, and worse prognosis 4, 2
• Thrombocytopenia correlates with renal disease and progression to end-stage renal disease 4, 2
• Severe leukopenia and lymphopenia significantly increase infection risk 4, 2

Inflammatory Markers

• Measure ESR at baseline for ongoing monitoring 2
• CRP has important clinical utility: significantly elevated CRP (>50 mg/L) suggests superimposed infection with 80-84% specificity, as SLE patients rarely have elevated CRP 4, 2

Renal Function Assessment

• Obtain serum creatinine, urinalysis with microscopy, and urine protein/creatinine ratio at baseline 4, 1, 2
• These tests provide prognostic information for renal involvement and end-stage renal disease 4, 2
• Patients with persistently abnormal urinalysis or raised serum creatinine should be considered for renal biopsy 4

Additional Baseline Tests

• Serum albumin indicates renal involvement and poor prognosis when low 4, 2

Testing Algorithm Summary

Follow this sequential approach:

1. Screen with ANA (1:160 dilution) only when clinical suspicion exists 1, 2
2. If ANA positive: Order anti-dsDNA (double-screening strategy), anti-ENA panel (Sm, Ro, La, RNP), antiphospholipid antibodies, C3/C4, CBC, renal function tests 1, 2
3. If ANA negative but high clinical suspicion: Proceed with anti-dsDNA testing and clinical follow-up 1

Common Pitfalls to Avoid

• Do not order ANA in patients with only nonspecific symptoms like malaise and fatigue—this leads to false positives 5
• Do not use classification criteria as diagnostic criteria—patients diagnosed with SLE may not fulfill classification criteria, and inappropriate use leads to underdiagnosis 4
• Avoid testing for lupus anticoagulant during acute thrombotic events or on full-dose anticoagulation, as interpretation is difficult 4
• Do not rely on a single positive antiphospholipid antibody test—confirmation after >12 weeks is mandatory 4

Monitoring After Diagnosis

• Monitor every 6-12 months in patients with inactive disease: CBC, ESR, CRP, serum albumin, creatinine, urinalysis 4, 2
• Repeat anti-dsDNA and complement levels at follow-up visits even if previously negative/normal 2
• More frequent monitoring required when reducing immunosuppressive therapy or in renal disease 2