Systemic Lupus Erythematosus Diagnosis

Essential Diagnostic Criteria

A positive antinuclear antibody (ANA) test at a titer ≥1:80 by indirect immunofluorescence on HEp-2 cells is the mandatory entry criterion for diagnosing SLE, as established by the 2019 EULAR/ACR classification criteria 1
In unselected populations, use a 1:160 dilution as the cut-off point for ANA detection to improve specificity 2
If ANA is negative at ≥1:80, SLE is effectively ruled out in most cases 1

When ANA is positive (≥1:80), proceed with the following laboratory tests, including anti-dsDNA testing using a double-screening strategy with solid-phase assay (SPA) such as FEIA and Crithidia luciliae immunofluorescence test (CLIFT) 1, 2, 4, 5
Additional autoantibody panel, including anti-Ro/SSA, anti-La/SSB, anti-RNP, and antiphospholipid antibodies, should be performed 6
Complement levels, including C3 and C4, should be measured as low levels support diagnosis 6
Hematologic tests, including complete blood count (CBC) for cytopenias, serum creatinine, and urinalysis with proteinuria quantification and urinary sediment, should be performed 6

The interpretation of anti-dsDNA results follows a hierarchy, with SPA positive + CLIFT positive indicating SLE is very likely, and SPA negative + CLIFT negative indicating SLE diagnosis cannot be established at this time 2, 3, 4, 5
The 2019 EULAR/ACR classification criteria require a positive ANA (≥1:80) as entry criterion and weighted scoring across multiple domains, including constitutional, hematologic, neuropsychiatric, mucocutaneous, serosal, musculoskeletal, and renal domains 1, 7, 8

For lupus nephritis, renal biopsy provides definitive diagnosis and prognostic information, and anti-C1q antibodies are found in almost 100% of patients with active lupus nephritis 4, 6
For neuropsychiatric lupus, diagnostic work-up should mirror that used in the general population presenting with the same neuropsychiatric manifestations, and brain MRI may provide prognostic information 6

Laboratories must include the method used in their reports, provide relevant clinical context beyond mere numbers, use international units (IU) when available for anti-dsDNA quantification, and validate results with clinical information when available 4, 8