Systemic Lupus Erythematosus

New classification criteria for systemic lupus erythematosus (SLE) from the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) represent a “paradigm shift” in how the disease is diagnosed and studied, the developers say. “The new criteria provide a simple, directed and highly accurate method for classifying SLE,” Dr. Sindhu Johnson from Toronto Western Hospital in Canada and co-authors note in Annals of the Rheumatic Diseases.

The 2019 EULAR/ACR classification criteria for SLE require an antinuclear antibody (ANA) titer of at least 1:80 on HEp-2 cells or an equivalent positive test at least once. If absent, the patient considered not to have SLE. If present, 22 “additive weighted” classification criteria considered. They clustered into seven separate clinical domains (constitutional, hematological, neuropsychiatric, mucocutaneous, serosal, musculoskeletal, renal) and three different immunologic domains (antiphospholipid antibodies, complement proteins, SLE-specific antibodies).

Systemic Lupus Erythematosus

A point system gives varying weight to each of the 22 criteria, with points ranging from 2 to 10. Patients accumulating 10 or more points are classified as having SLE. A finding of class III or IV lupus nephritis on renal biopsy carries the most weight (10 points) and in the presence of a positive ANA is enough to classify a patient as Systemic Lupus Erythematosus. Renal biopsy with class II or V lupus nephritis still carries a large weight (eight points); but is not by itself sufficient for the classification of SLE, the authors say.

The new criteria also for the first time include unexplained fever as a criterion; which turned out to be “common and remarkably characteristic for SLE,” the developers say. “However, since infections are a major cause of death in SLE, it is of utmost importance to stress that fever; like all other criteria manifestations, should only counted if no better explanation exists; and that infections have to be suspected first in any patient with (potential) SLE, particularly when CRP elevated,” they write. The new classification criteria validated against a large number of cases, including many patients; with manifestations that resemble SLE but who do not have SLE, the authors note.

Molecular classification criteria

“In the validation cohort, the new criteria had a sensitivity of 96.1% and specificity of 93.4%; compared with 82.8% sensitivity and 93.4% specificity of the ACR 1997 and 96.7% sensitivity and 83.7% specificity of the Systemic Lupus International Collaborating Clinics 2012 criteria,” they report. Molecular classification criteria also considered during the development process. Many novel biomarkers nominated, but they were all “voted out” by the expert panel largely; because of limited availability in the clinical setting and/or insufficient evidence, the authors report.

“However, inclusion of novel biomarkers, beyond autoantibodies; may ultimately further improve the specificity of SLE classification; increase alignment of classification with underlying disease pathogenesis; and improve the performance and information content of clinical trials.  Thus, testing of biomarkers against these criteria is an important area for future research,” the writers say. An electronic app is being developed to help clinicians use the new criteria. The authors anticipate that other groups will test these criteria, “which will constitute important external validation.