What is the workup for Systemic Lupus Erythematosus (SLE)?

From the Guidelines

The workup for Systemic Lupus Erythematosus (SLE) should include a comprehensive panel of laboratory tests alongside a thorough clinical evaluation, as recommended by the most recent guidelines 1. The initial step involves a complete blood count, comprehensive metabolic panel, urinalysis, and inflammatory markers (ESR, CRP).

• Specific autoantibody tests should be ordered, including ANA (antinuclear antibody), which is positive in 95% of SLE patients, followed by more specific antibodies if ANA is positive: anti-dsDNA, anti-Smith, anti-Ro/SSA, anti-La/SSB, and anti-RNP.
• Complement levels (C3, C4) should also be checked, as they are typically low in active disease.
• Antiphospholipid antibodies (anticardiolipin, lupus anticoagulant, anti-β2 glycoprotein I) should be assessed to evaluate thrombotic risk. Additional testing may include:
• A chest X-ray, ECG, and possibly echocardiogram to evaluate cardiopulmonary involvement.
• Renal function assessment, potentially including 24-hour urine protein and creatinine clearance.
• A kidney biopsy may be necessary if nephritis is suspected. This comprehensive approach is essential because SLE is a multi-system disease with variable presentation, and accurate diagnosis requires meeting classification criteria that combine clinical features with laboratory findings, as supported by recent studies 1. Early diagnosis allows for prompt treatment to prevent organ damage and improve long-term outcomes, highlighting the importance of a thorough workup in managing SLE, as emphasized in the 2019 update of the EULAR recommendations 1.

From the Research

Clinical Factors

• The 2019 European Alliance of Associations for Rheumatology/American College of Rheumatology classification criteria for SLE include clinical factors such as fever, cytopenia, rash, arthritis, and proteinuria, which may be indicative of lupus nephritis 2
• Cytopenia is a common hematological disorder in SLE patients, with anemia, leukopenia, lymphopenia, neutropenia, and thrombocytopenia being detected in 56.1%, 28.9%, 76%, 4.5%, and 17.2% of patients, respectively 3
• Photosensitivity, renal involvement, and antiphospholipid syndrome (APS) are more frequently detected in patients with cytopenia at the time of diagnosis 3

Immunologic Measures

• The 2019 European Alliance of Associations for Rheumatology/American College of Rheumatology classification criteria for SLE include immunologic measures such as SLE-specific autoantibodies and low complement levels 2
• Antinuclear antibody (ANA) and anti-double-stranded DNA (ds-DNA) antibody are commonly used in the diagnosis of SLE, with sensitivities of 91.75% and 67.01%, and specificities of 79.65% and 98.23%, respectively 4
• Complement C3 and C4 levels are also used in the diagnosis of SLE, with sensitivities of 87.11% and 88.66%, and specificities of 82.74% and 77.43%, respectively 4

Diagnostic Criteria

• The American College of Rheumatology (ACR) criteria for the diagnosis of SLE include a combination of clinical and immunologic factors 5
• The combined detection of ANA, anti-ds-DNA antibody, and complements C3 and C4 can play a complementary role in the diagnosis and treatment of SLE patients, with a sensitivity and specificity of 97.42% and 80.97%, respectively 4

Laboratory Tests

• Erythrocyte sedimentation rates (ESR) are higher in patients with cytopenia at the time of diagnosis 3
• C3 and C4 hypocomplementemia is more prevalent in patients with cytopenia at the time of diagnosis 3
• Anti-ds-DNA antibody levels can fluctuate widely and reflect disease activity, whereas anti-RBP antibody levels tend to be stable 6