Successive SLE Classification Systems May Help Clarify Mysterious Disease

Investigators note that the most recent systemic lupus erythematosus (SLE) classification system has quickly become the gold standard, but disease classification remains challenging.

Classifying patients with systemic lupus erythematosus (SLE) can be challenging, but a new review article notes that the classification tools at the disposal of physicians have gotten significantly better over the past 40 years.

The article, published in Journal of Autoimmunity, traces the history of SLE classification to 1982, when the American College of Rheumatology (ACR) released the first major set of classification criteria. The authors noted there have since been 3 new versions of the criteria.

The ACR criteria were updated in 1997. In 2012, the Systemic Lupus International Collaborating Clinics (SLICC) criteria were first published. Most recently, the European League Against Rheumatism and ACR jointly released the EULAR/ACR criteria in 2019, which the authors said has become the gold standard inclusion criteria for SLE clinical trials. Combined, the classification systems have had a major impact on patient care.

“Beyond providing a necessary tool in defining a set of SLE patients for clinical trials, observational and translational studies on SLE, the criteria have also continuously shaped our picture of the disease,” the authors wrote.

Still, they said several gaps remain, and SLE continues to be a diagnostic challenge.

“From the ACR 1982 criteria through the EULAR/ACR 2019 criteria it has held true that we do not have a unique laboratory parameter that defines who has SLE,” they said.

The biomarker of antinuclear antibodies (ANA), they wrote, has the sensitivity but not the specificity to identify most patients with SLE. Anti–double-stranded DNA antibodies can identify most patients, but the marker leaves out about a quarter of people who have SLE, they said. Other potential markers, like low levels of C3 or C4 proteins and type I interferon signature, also have drawbacks, including issues of availability and standardization, the authors said.

On the other hand, the investigators said there are known pathogenic antibodies that indicate organ manifestations. The Coombs test can be a good indicator of autoimmune hemolytic anemia, although other antibody-to-manifestation links are more complicated, they said.

In addition, the study investigators said it is important to remember that physicians diagnosing SLE need to rule out other possible causes of apparent SLE.

“[At] least some objective test for autoimmunity needs to be positive to not take something for SLE that is in fact from a different (ie, nonautoimmune) sphere,” they wrote.

The SLICC criteria include a broad battery of possible immunological tests, they said, but the EULAR/ACR criteria rely on positive ANA, which the authors said is “a much simpler way” of achieving the same goal. They said the criteria for diagnosing SLE have grown and matured over time, with the EULAR/ACR criteria representing the most advanced method of not only classifying SLE but also predicting SLE severity.

“The 2019 EULAR/ACR criteria have been broadly validated and adopted into clinical trials in the short time since their full publication,” the authors said.

Yet, even though they describe this evolution as a success story, they said no system can be treated as a totally independent diagnostic tool.

“[It] is important to reiterate that classification criteria are not what should decide on the individual diagnosis in a patient,” they wrote, noting that the systems are meant to work on a group level, rather than an individual level.

“In consequence, there will be individual patients with SLE who do not fulfill the classification criteria, but still should be diagnosed with SLE to receive proper treatment,” they wrote.


Aringer M, Costenbader K, Dörner T, Johnson SR. Advances in SLE classification criteria. J Autoimmun. Published online June 17, 2022. doi:10.1016/j.jaut.2022.102845

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