From the Guidelines
Lupus diagnosis should be based on a combination of clinical symptoms, physical examination, and laboratory tests, with a positive antinuclear antibody (ANA) test at a titer ≥1:80 by the indirect immunofluorescence test on HEp-2 cells (IFI) as a required entry criterion, as per the EULAR/ACR 2019 classification criteria 1.
Key Considerations
- The EULAR/ACR 2019 classification criteria require a positive ANA test as an entry criterion, which has improved the performance of the criteria as a classification system, but makes caution necessary when used in diagnosis due to its relatively low specificity of 74.7% (IC 95%: 66.7% - 81.3%) 1.
- Additional blood tests, such as anti-double-stranded DNA antibodies, anti-Smith antibodies, complement levels, complete blood count, and kidney and liver function tests, may be necessary to support the diagnosis.
- A comprehensive evaluation by a rheumatologist is essential, as lupus can mimic many other conditions.
Diagnostic Process
- The diagnostic process often takes time, sometimes months or years, as symptoms may develop gradually.
- Early diagnosis is crucial for proper management and to prevent organ damage, so patients with persistent unexplained symptoms like joint pain, skin rashes, and fatigue should seek medical evaluation promptly.
- The use of anti-dsDNA autoantibodies in the diagnosis and follow-up of systemic lupus erythematosus is recommended, with international standards and likelihood ratios used to harmonize laboratory test results across assays 1.
Important Laboratory Tests
- ANA test: usually the first screening test performed, with over 95% of lupus patients testing positive, though a positive result alone is not diagnostic.
- Anti-double-stranded DNA antibodies: associated with lupus nephritis and leukopenia, and may be used to support the diagnosis.
- Complement levels: may be used to support the diagnosis and monitor disease activity.
- Complete blood count: may be used to support the diagnosis and monitor disease activity.
- Kidney and liver function tests: may be used to support the diagnosis and monitor disease activity.
From the Research
Lupus Diagnosis
- The diagnosis of systemic lupus erythematosus (SLE) can be facilitated by the detection of anti-nuclear antibody (ANA), anti-double-stranded DNA (ds-DNA) antibody, and complements C3 and C4 2.
- The sensitivity and specificity of ANA in diagnosing SLE were 91.75% and 79.65%, respectively, while those of anti-ds-DNA antibody were 67.01% and 98.23%, respectively 2.
- The combined diagnosis of SLE with ANA, anti-ds-DNA antibody, complement C3, and C4 can play a complementary role in the diagnosis and treatment of SLE patients 2.
Autoantibodies in Lupus Diagnosis
- High baseline anti-double-stranded DNA and anti-histone levels in immune complexes associated with attainment of zero scores in clinical SLE disease activity index 2000 during the 24-month follow-up 3.
- Serum levels of most autoantibodies had declined at month 3, whereas autoantibody levels in immune complexes, except for anti-double-stranded DNA, showed a more gradual decline over 1-2 years 3.
- Anti-ds-DNA antibodies are mainly restricted to SLE, but can also be found in non-SLE patients who fulfill several of the ARA criteria for SLE 4.
Sensitivity and Specificity of Autoantibodies
- The sensitivity and specificity of ANA and anti-ds-DNA in the diagnosis of SLE were high, even when using sera from patients with multiple medical problems as controls 5.
- The specificity of anti-ds-DNA was 100% and 97% when using sera from healthy controls and patients with multiple medical problems, respectively 5.
- Elevated subclinical double-stranded DNA antibodies were associated with future proliferative lupus nephritis, and the rate of increase in anti-ds-DNA antibody level was most specific for proliferative lupus nephritis 6.