Laboratory Workup for Systemic Lupus Erythematosus
The European League Against Rheumatism (EULAR) recommends a comprehensive baseline autoantibody panel including ANA, anti-dsDNA, anti-Ro, anti-La, anti-RNP, anti-Sm, anti-phospholipid antibodies, C3, and C4, combined with routine laboratory assessments including complete blood count, ESR, CRP, serum albumin, serum creatinine (or eGFR), urinalysis, and urine protein/creatinine ratio. 1, 2
Initial Autoantibody Panel
Core Serologic Tests at Baseline:
ANA (Antinuclear Antibody): The most sensitive screening test for SLE; an ANA titer ≥1:40 with characteristic multiorgan involvement can establish diagnosis, while titers <1:40 usually rule out SLE 3, 4. Higher ANA titers >1:640 predict disease flares (odds ratio 7.6) 5.
Anti-dsDNA antibodies: Correlate with disease activity and active renal disease; useful for monitoring disease progression 1, 2.
Anti-Sm antibodies: Highly specific for SLE with strong confirmatory power; part of baseline diagnostic panel 1, 4.
Anti-Ro (SSA) and Anti-La (SSB) antibodies: Essential for prognostic assessment and must be checked before pregnancy due to neonatal lupus risk 1, 2.
Anti-RNP antibodies: Provide prognostic information 1.
Anti-phospholipid antibodies: Associated with thrombotic manifestations, damage development, and pregnancy complications 1, 2.
Complement Levels
- C3 and C4: Essential baseline measurements; low levels (particularly C3) predict flares and correlate with active disease, especially renal involvement 1, 2. Complement levels sometimes associate with active disease but have no predictive value for flare development 1.
Routine Laboratory Assessments
Hematologic Parameters:
- Complete Blood Count (CBC): Essential for detecting cytopenias 1, 2. Severe anemia associates with organ involvement and worse prognosis 1, 2. Thrombocytopenia correlates with renal disease and progression to end-stage renal disease 1, 2. Severe leukopenia and lymphopenia increase infection risk 1, 2.
Inflammatory Markers:
ESR (Erythrocyte Sedimentation Rate): Recommended at baseline and for monitoring 1, 2.
CRP (C-reactive protein): Patients with SLE rarely have elevated CRP during disease flares; significantly elevated CRP (>50 mg/L) suggests superimposed infection and should prompt evaluation for bacterial infection 1, 2.
Renal Function Assessment:
Serum creatinine (or eGFR): Provides prognostic information about renal involvement 1, 2.
Serum albumin: Low levels indicate renal involvement and poor prognosis 1, 2.
Urinalysis with urine protein/creatinine ratio: Essential for detecting and monitoring nephritis 1, 2. Patients with persistently abnormal urinalysis or elevated creatinine should have urine microscopy and be considered for renal biopsy 1.
Selective Re-evaluation of Autoantibodies
Anti-phospholipid antibodies should be re-evaluated:
- Prior to pregnancy, surgery, or transplant 1
- Before use of estrogen-containing treatments 1
- With new neurological or vascular events 1
Anti-Ro and Anti-La antibodies should be re-evaluated:
- Before pregnancy 1
Anti-dsDNA and complement (C3/C4):
- May support evidence of disease activity or remission 1
Ongoing Monitoring Schedule
For patients with inactive disease, assess every 6-12 months:
- Complete blood count 1
- Erythrocyte sedimentation rate 1
- C-reactive protein 1
- Serum albumin 1
- Serum creatinine (or eGFR) 1
- Urinalysis and urine protein/creatinine ratio 1
For patients with established nephropathy, assess every 3 months for the first 2-3 years:
- Protein/creatinine ratio (or 24-hour proteinuria) 1
- Immunological tests (C3, C4, anti-dsDNA) 1
- Urine microscopy 1
- Blood pressure 1
Critical Pitfalls to Avoid
Do not order ANA testing indiscriminately: Due to low disease prevalence in primary care, ANA has low predictive value without typical clinical symptoms. Only order when patients have unexplained involvement of two or more organ systems 3.
Do not assume elevated CRP indicates lupus flare: In SLE patients, significantly elevated CRP (>50 mg/L) should prompt evaluation for superimposed bacterial infection rather than disease activity 1, 2.
Do not rely solely on anti-dsDNA/complement for flare prediction: While these markers correlate with disease activity, they have limited ability to predict treatment response and should be used only as supplemental information 1.