From the Guidelines
ANA-negative lupus should be diagnosed and managed based on clinical symptoms, other laboratory findings, and additional autoantibody tests, as a negative ANA result does not rule out the disease. According to the European League Against Rheumatism recommendations 1, the assessment of patients with systemic lupus erythematosus (SLE) must include the evaluation of disease activity, organ damage, general quality of life, comorbidities, and drug toxicity.
Key Considerations
- The diagnosis of SLE requires a panel of specific laboratory tests, including ANA, anti-dsDNA, and anti-ENA antibodies 1.
- ANA testing is primarily intended for diagnostic purposes, and not for monitoring disease progression 1.
- The detection of ANA is the first level test for laboratory diagnosis of SLE, and the indirect immunofluorescent assay (IIFA) is the reference method for ANA screening 1.
- In cases of high clinical suspicion, the physician should request determination of antibodies to specific ENA, irrespective of the result of the ANA test 1.
Management
- Treatment for ANA-negative lupus follows the same approach as ANA-positive cases, including NSAIDs for mild symptoms, antimalarials like hydroxychloroquine for skin and joint issues, and immunosuppressants for more severe manifestations.
- Corticosteroids may be used during flares, and regular monitoring of kidney function, blood counts, and other affected systems is essential to prevent significant organ damage.
- The frequency of assessments should be every 6-12 months in patients with no activity, no damage, and no comorbidity, with an emphasis on preventive measures 1.
Laboratory Assessment
- The monitoring of autoantibodies and complement, including ANA, anti-dsDNA, anti-Ro, anti-La, anti-RNP, anti-Sm, anti-phospholipid, C3, and C4, is recommended at baseline and during follow-up 1.
- Re-evaluation of previously negative patients for anti-phospholipid antibodies, anti-Ro, and anti-La antibodies is recommended in certain situations, such as prior to pregnancy or surgery 1.
From the Research
Definition and Prevalence of ANA Negative Lupus
- ANA negative lupus refers to a condition where patients with systemic lupus erythematosus (SLE) test negative for antinuclear antibodies (ANAs) 2, 3, 4.
- The prevalence of ANA negative SLE is relatively low, with one study reporting a prevalence of 2.11% in a large single-center SLE inception cohort 4.
- Another study found that 36.9% of patients with cutaneous lupus erythematosus (CLE) had a negative ANA test, and 18.0% of these patients met the criteria for SLE using the American College of Rheumatology (ACR) and/or Systemic Lupus International Collaborating Clinics (SLICC) criteria 3.
Clinical Characteristics of ANA Negative Lupus
- ANA negative SLE patients often have different clinical characteristics compared to ANA positive SLE patients, including a higher prevalence of thrombocytopenia, low complement, and positive anti-double-stranded DNA (anti-dsDNA) 4.
- These patients may also have a higher prevalence of medium-high titer anti-cardiolipin antibody (aCL) IgG and anti-ß2 glycoprotein I (anti-ß2GPI) compared to ANA positive SLE patients 4.
- The diagnosis of ANA negative SLE can be challenging, and clinicians should consider testing for complement, anti-dsDNA, and antiphospholipid antibody (aPL) in patients with rheumatic symptoms, particularly thrombocytopenia 4.
Diagnosis and Testing
- The ANA test is a key diagnostic tool for SLE, but it is not specific for this disease and must be interpreted in the appropriate clinical context 5.
- ANA staining patterns and more specific autoantibody testing may be helpful in the diagnosis of suspected SLE or ANA-associated disease 5.
- A combination of two quantitative methods and the ANA pattern is the most efficient strategy for detecting anti-dsDNA antibodies in SLE patients 6.
- Clinicians should be aware of the limitations of ANA testing, particularly in patients with nonspecific symptoms, and consider other diagnostic tests and clinical evaluations to confirm a diagnosis of SLE 5.