Diagnostic Workup for Systemic Lupus Erythematosus (SLE)
The diagnostic workup for SLE should include a comprehensive panel of autoantibodies, complete blood count, urinalysis, and specific organ assessments based on clinical manifestations to establish diagnosis and evaluate disease activity and organ involvement. 1
Initial Laboratory Evaluation
Essential Laboratory Tests
Autoantibody Profile:
- Antinuclear antibodies (ANA) - primary screening test
- Anti-double-stranded DNA (anti-dsDNA) - high specificity for SLE
- Anti-Smith (anti-Sm) antibodies - highly specific for SLE
- Anti-Ro/SSA and anti-La/SSB antibodies - associated with neonatal lupus risk
- Antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, anti-β2-glycoprotein I) - associated with thrombotic events 2
Complement Levels:
- C3 and C4 complement - low levels suggest active disease
- CH50 - total complement activity 2
Complete Blood Count:
- Evaluate for cytopenias (anemia, leukopenia, thrombocytopenia)
- These findings have prognostic value for organ involvement and disease progression 2
Renal Function Tests:
Inflammatory Markers:
- Erythrocyte sedimentation rate (ESR)
- C-reactive protein (CRP) - note that CRP is often normal in SLE flares without infection 2
Organ-Specific Evaluation
Cutaneous Assessment
- Skin biopsy with immunofluorescence for suspected cutaneous lupus
- Consider using Cutaneous Lupus Disease Area and Severity Index (CLASI) for patients with predominant skin manifestations 2
Renal Assessment
- Kidney biopsy should be considered in patients with:
Neuropsychiatric Assessment
- The diagnostic workup for neuropsychiatric manifestations should be similar to that in the general population with the same symptoms 2
- Consider:
- Cerebrospinal fluid analysis (to exclude CNS infection)
- Brain MRI (T1/T2, FLAIR, diffusion-weighted imaging, enhanced T1 sequence)
- EEG (for seizure disorders)
- Neuropsychological testing (for cognitive dysfunction) 2
Cardiovascular Assessment
- Echocardiogram (for valvular disease, pericarditis)
- ECG (for conduction abnormalities)
- Assessment of cardiovascular risk factors (blood pressure, lipid profile, glucose) 2
Disease Activity and Damage Assessment
Disease Activity Measurement
- Use validated disease activity indices such as:
- SLEDAI (SLE Disease Activity Index)
- BILAG (British Isles Lupus Assessment Group)
- SLAM (Systemic Lupus Activity Measure) 2
Damage Assessment
- Annual assessment using Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index 2
Diagnostic Criteria
The 2019 EULAR/ACR classification criteria can guide diagnosis, requiring:
- Positive ANA (≥1:80 by immunofluorescence) as entry criterion
- Additional clinical and immunological criteria with weighted scoring system 1, 3
Common Pitfalls and Caveats
False-negative ANA: While rare, SLE can present with negative ANA initially. Consider repeat testing if clinical suspicion is high 4
Infection vs. Flare: Distinguishing between infection and disease flare can be challenging. Very high CRP (>50 mg/L) suggests infection rather than SLE flare 2
Neuropsychiatric Attribution: Neuropsychiatric symptoms may be due to SLE, medications, infections, or other causes. Thorough evaluation is needed before attributing to SLE 2
Monitoring Frequency: Laboratory monitoring should be more frequent during active disease or treatment changes, and can be less frequent during stable disease 2
Drug-induced Lupus: Consider medication review as certain drugs can induce lupus-like syndromes 5
Follow-up Monitoring
- Disease activity assessment at each visit
- Annual damage assessment
- Quality of life evaluation
- Comorbidity screening
- Drug toxicity monitoring 2
Regular monitoring for specific organ involvement and comorbidities is essential for early detection of disease progression and complications, which directly impacts morbidity, mortality, and quality of life in patients with SLE.