Evidence suggests that the complex nature of systemic lupus erythematosus (SLE) makes it difficult for clinicians to diagnose the autoimmune disease. With two SLE classification criteria currently in use, the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR) joined together to create a comprehensive classification criteria, led by Sindhu R. Johnson, MD, PhD, FRCPC. “There have been changes in our understanding of the classification of SLE, so new criteria should reflect these changes,” notes Dr. Johnson.
The new set of criteria were developed over four phases using data and expert-based methods. The process was overseen by a 12-member steering committee selected by EULAR and ACR. In Phase I, the researchers identified 43 criteria candidates through review of the literature, a Delphi survey of international experts, a survey of patients. and evaluation of data from an international cohort of patients. In Phase II, candidate criteria were reduced to 20 through consensus of international SLE experts and evaluations of the performance characteristics of each criterion. Each criterion was defined and an international SLE expert panel assigned it a particular weight in Phase III (Table). Phase IV focused on fine-tuning the criteria through a derivation cohort and testing of the criteria in a validation cohort of international SLE patients and patients with conditions similar to SLE.
A Weighted System
An international SLE expert panel derived numeral weights to each of the criteria. “The criteria fall under seven clinical domains: constitutional symptoms, hematologic, neuropsychiatric, mucocutaneous, serosal, musculoskeletal, renal; and three immunologic domains: antiphospholipid, complement proteins, and SLE-specific antibodies,” explains Dr. Johnson. “Each criterion is assigned a score or weight. Within each domain only the highest score is counted. A score is determined by adding the points or weights. A patient is classified as SLE if they have a total score of 10 or more points.” Weights are assigned by how important or informative the disease manifestations are in classifying SLE. “For example, lupus nephritis is more unique to SLE than oral ulcers,” notes Dr. Johnson. “Previous scoring systems weighted criteria equally. This system explicitly indicates the relative importance of each criterion to the classification of SLE.” For example, Class III or IV lupus nephritis has a weight of 10 points. A patient can be classified with SLE with this criterion and a positive antinuclear antibody (ANA).
Along with previously used criteria, the new classification criteria include ANA—regularly used by clinicians as a screening test—as an entry criterion. While fever has been added as a new and early identifying criteria for SLE, it is noted, however, that other causes of fever need to be ruled out.
A New Perspective on Criteria
Dr. Johnson highlights that the new set of classification criteria were developed for research purposes (Table). “The diagnosis of SLE remains in the judgement of appropriately trained physicians,” he adds. “The lack of fulfilling classification criteria should not preclude a diagnosis and should not be used as justification to deny a patient appropriate therapy.” The criteria were developed to inform how clinicians and researchers think of SLE. The weighted criteria focus on disease manifestations and how they contribute to the classification to SLE. Dr. Johnson warns that the criteria should not be attributed to SLE if there is a more likely explanation.
“The use of classification criteria in SLE is not new, but the way we think about classification criteria in SLE is a paradigm shift,” explains Dr. Johnson. “The use of ANA as an entry criterion, the weighting of disease manifestations, hierarchical clustering of manifestations within a domain, and the use of an additive numeric point system are all novel features. This system nicely balances sensitivity and specificity. It is effective in classifying both early and established disease.”
2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus