What investigations are used for the diagnosis of Systemic Lupus Erythematosus (SLE)?

From the Guidelines

The diagnosis of Systemic Lupus Erythematosus (SLE) should be approached with a comprehensive set of investigations, starting with anti-nuclear antibody (ANA) testing, followed by more specific antibodies such as anti-double stranded DNA (anti-dsDNA), anti-Smith (anti-Sm), anti-Ro/SSA, anti-La/SSB, and anti-ribonucleoprotein (anti-RNP) if ANA is positive, as recommended by recent guidelines 1.

Initial Testing

Initial testing should include:

• Complete blood count to identify anemia, leukopenia, lymphopenia, or thrombocytopenia
• Inflammatory markers like ESR and CRP, which are typically elevated
• Autoantibody testing, with ANA being the most sensitive test, though not specific

Autoantibody Testing

If ANA is positive, more specific antibodies should be tested, including:

• Anti-double stranded DNA (anti-dsDNA)
• Anti-Smith (anti-Sm)
• Anti-Ro/SSA
• Anti-La/SSB
• Anti-ribonucleoprotein (anti-RNP) As suggested by the international recommendations for the assessment of autoantibodies to cellular antigens referred to as anti-nuclear antibodies 1.

Complement Levels and Urinalysis

Complement levels (C3, C4) are often decreased due to consumption during active disease. Urinalysis and renal function tests are essential to detect lupus nephritis, looking for proteinuria, hematuria, and cellular casts.

Imaging Studies and Biopsies

Imaging studies like chest X-ray and echocardiogram may be needed to assess organ involvement. Skin or kidney biopsies can confirm tissue damage and inflammation patterns specific to SLE.

Classification Criteria

These investigations, combined with clinical features, help fulfill the SLICC or ACR classification criteria used for diagnosis, which require multiple clinical and immunological criteria to be met, as outlined in recent recommendations for the use of anti-dsDNA autoantibodies in the diagnosis and follow-up of SLE 1.

Key Recommendations

• ANA testing should be the first step in autoantibody testing 1
• If ANA is positive, testing for anti-dsDNA antibodies is advised when there is clinical suspicion of SLE 1
• The method used for anti-dsDNA antibody detection should be included in the test result 1
• A double-screening strategy using a last-generation SPA in the first place and, subsequently, the CLIFT as the confirmation test is recommended for anti-dsDNA testing 1

From the Research

Investigations for Diagnosis of Systemic Lupus Erythematosus (SLE)

The diagnosis of SLE involves a combination of clinical symptoms, laboratory findings, and optional biopsy results. Some of the key investigations used for the diagnosis of SLE include:

• Antinuclear antibody (ANA) test: This is the most sensitive test for SLE and is used as a screening assay to rule out its presence 2
• Anti-native (N)-DNA and anti-Sm (Smith antigen) tests: These tests are highly specific for SLE and have strong confirmatory powers 2
• Farr anti-DNA precipitate immunoassay: This test is sensitive and specific, and correlates well with the clinical condition of the patient 3
• Measurement of antibodies to DNA: This test is useful in monitoring disease activity and may contribute to earlier diagnosis and more precise management of SLE patients 3
• Assessment of autoantibodies: Including nucleosome, double-stranded DNA (dsDNA), Smith, ribonucleoprotein, and Sjögren's syndrome-related antigens, which can help in evaluating disease activity, damage accrual, and SLE-related clinical and serological manifestations 4

Laboratory Tests and Indices

The following laboratory tests and indices are currently used in standard clinical care and in clinical research for the diagnosis of SLE:

• LE cell test: Although once used as the laboratory basis for SLE diagnosis, it is now considered insensitive, non-specific, and does not correspond to clinical activity of the patient 3
• Antinuclear-antibody detection: Although very sensitive, it is not specific for SLE and its value is limited for use as a screening technique to rule out SLE 3
• Systemic Lupus Erythematosus Disease Activity Index 2000: This index is used to evaluate disease activity 4
• Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI): This index is used to evaluate disease-related damage 4