From the Guidelines
Systemic Lupus Erythematosus (SLE) is diagnosed using the European League Against Rheumatism (EULAR) and American College of Rheumatology (ACR) 2019 classification criteria, which require a positive antinuclear antibody (ANA) test at a titer ≥1:80 by indirect immunofluorescence on HEp-2 cells as an entry criterion. The diagnosis of SLE involves a combination of clinical and laboratory criteria, including clinical manifestations such as malar rash, discoid rash, photosensitivity, oral ulcers, arthritis, serositis, kidney disorder, neurologic disorder, and hematologic disorders, as well as laboratory tests such as positive ANA, anti-double-stranded DNA antibodies, anti-Smith antibodies, antiphospholipid antibodies, low complement levels, and direct Coombs test 1.
The EULAR/ACR 2019 classification criteria have improved the performance of the criteria as a classification system, but caution is necessary when using them for diagnosis due to the relatively low specificity of ANA detection 1. The use of anti-dsDNA autoantibodies in the diagnosis and follow-up of SLE is also important, but their determination still lacks proper standardization, and their diagnostic performance changes depending on the population under study 1.
Key points to consider in the diagnosis of SLE include:
- A positive ANA test at a titer ≥1:80 by indirect immunofluorescence on HEp-2 cells is required as an entry criterion 1
- Clinical manifestations such as malar rash, discoid rash, photosensitivity, oral ulcers, arthritis, serositis, kidney disorder, neurologic disorder, and hematologic disorders are important criteria 1
- Laboratory tests such as positive ANA, anti-double-stranded DNA antibodies, anti-Smith antibodies, antiphospholipid antibodies, low complement levels, and direct Coombs test are also important criteria 1
- The use of anti-dsDNA autoantibodies in the diagnosis and follow-up of SLE requires careful interpretation of results due to the heterogeneity of these antibodies and the lack of standardization in their determination 1
In clinical practice, the diagnosis of SLE typically involves a thorough medical history, physical examination, and various blood tests to detect autoantibodies and assess organ function, as well as additional testing such as kidney or skin biopsies to confirm organ involvement 1. The EULAR/ACR 2019 classification criteria provide a useful framework for diagnosing SLE, but physicians must evaluate the complete clinical picture and use their clinical judgment to make a diagnosis.
From the Research
Diagnostic Criteria for Systemic Lupus Erythematosus (SLE)
The diagnostic criteria for SLE are based on a combination of clinical presentations and traditional lab testing, including:
- Clinical manifestations such as skin lesions, arthritis, renal disorder, neurologic disorder, hematologic changes, and others 2
- Serum anti-nuclear antibody, anti-ds-DNA antibody, and anti-Sm antibody as important biomarkers of SLE patients 2
- The American College of Rheumatology (ACR) criteria, which have undergone several changes since their introduction in 1971 2
- The Systemic Lupus Collaborating Clinics (SLICC) criteria, proposed in 2012, which include new knowledge of autoantibodies and the importance of low complement 2
- The 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria, which rely on clinical and routine immunological items, including anti-nuclear antibodies (ANA) as an obligatory entry criterion 3
Limitations of Current Diagnostic Criteria
The current diagnostic criteria for SLE have suboptimal sensitivity and specificity, and are unable to indicate disease cause or guide physicians in decision-making for treatment 4
- Individual biomarkers lack sensitivity or specificity, and many emerging biomarkers have not been carefully validated for clinical use 4
- The lack of a more molecular approach to diagnosis is a limitation of current criteria, and a more uniform molecular approach will not be feasible until the molecular mechanisms underlying the tendency toward producing multiple autoantibodies are better understood 3
Future Directions
The development of new biomarkers and diagnostic panels is needed to improve the diagnosis and treatment of SLE 4
- Emerging molecular markers, such as those from blood, urine, cerebrospinal fluids (CSF), and other bodily fluids, may be useful in distinguishing SLE from other diseases and in monitoring disease activity 4
- A more accurate and robust tool for effective clinical management and drug development in lupus patients is urgently needed 4