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

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Last updated: April 26, 2025View editorial policy

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From the Guidelines

The workup for lupus (systemic lupus erythematosus or SLE) involves a comprehensive approach combining clinical assessment, laboratory testing, and sometimes imaging studies, with the most recent and highest quality study recommending a thorough history and physical examination, focusing on characteristic symptoms like joint pain, skin rashes, and fatigue 1. The initial step in the workup for lupus should include a thorough history and physical examination, focusing on characteristic symptoms like joint pain, skin rashes (particularly the malar "butterfly" rash), photosensitivity, oral ulcers, and fatigue.

  • Laboratory testing should include:
    • Complete blood count (looking for cytopenias)
    • Comprehensive metabolic panel
    • Urinalysis (to assess for proteinuria or hematuria)
    • Erythrocyte sedimentation rate and C-reactive protein (inflammatory markers)
    • Specific autoantibody tests, including antinuclear antibody (ANA), anti-double-stranded DNA antibody, anti-Smith antibody, anti-Ro/SSA, anti-La/SSB, and antiphospholipid antibodies
  • Complement levels (C3 and C4) are often decreased in active lupus, and additional testing may include chest X-ray, echocardiogram to evaluate for pericardial or valvular involvement, and renal function tests.
  • If kidney involvement is suspected, a renal biopsy may be necessary to determine the type and extent of lupus nephritis, as recommended by the European League Against Rheumatism 1. The diagnosis is ultimately made using the American College of Rheumatology or Systemic Lupus International Collaborating Clinics classification criteria, which require a combination of clinical and immunological findings, and early referral to a rheumatologist is essential for confirming the diagnosis and establishing appropriate treatment, with the use of anti-dsDNA autoantibodies being an important tool in the diagnosis and follow-up of SLE 1.
  • The use of anti-dsDNA autoantibodies in the diagnosis and follow-up of SLE has been recommended by an expert panel, with a quantitative assay being used to monitor disease activity, and the CLIFT assay being used for confirmation purposes and to ascertain a potential clinical correlation 1.
  • A standardized core set of variables for the assessment of patients with SLE in routine clinical practice has been developed, including patient assessment, cardiovascular risk factors, other risk factors, infection risk, frequency of assessments, laboratory tests, mucocutaneous involvement, kidney monitoring, neuropsychological manifestations, and ophthalmology assessment, as recommended by the European League Against Rheumatism 1.

From the Research

Workup for Lupus

To work up lupus, the following steps can be taken:

  • Accurate physical and laboratory diagnosis, as described in 2
  • Monitoring of disease activity, which can include assessing serum levels of anti-dsDNA, anti-nucleosome, anti-C1q, and anti-histone antibodies, as discussed in 3
  • Recording of accumulated organ morbidity, as mentioned in 2
  • Integration of these assessments with the patient's own perceptions of health status and quality of life, as noted in 2

Laboratory Tests

The following laboratory tests can be used to work up lupus:

  • Anti-dsDNA antibodies, which have been shown to be correlated with SLE disease activity, as discussed in 3
  • Anti-nucleosome antibodies, which can be used to diagnose active lupus nephritis and monitor SLE disease activity, as described in 3
  • Anti-C1q antibodies, which can be used to diagnose active lupus nephritis and monitor SLE disease activity, as discussed in 3
  • Anti-histone antibodies, which can be used to diagnose active lupus nephritis and monitor SLE disease activity, as described in 3

Clinical Practice Guidelines

Clinical practice guidelines can provide guidance on the diagnosis, monitoring, and treatment of lupus, as discussed in 4. However, the methodological quality and recommendations of these guidelines can vary substantially, highlighting the need for collaborative and multidisciplinary efforts to develop comprehensive, high-quality evidence-based guidelines.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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