Two-Dimensional Approach Leads to Significant Revisions of LE Classifications

A re-evaluation of patients found most had intermediate lupus erythematosus, even though the vast majority were initially diagnosed with the limited-cutaneous form of the disease.

A new report suggests many cases of lupus erythematosus (LE) are incorrectly classified as limited-cutaneous LE when in fact they are systemic.

Corresponding author Mirjana Ziemer, MD, of Germany’s University Hospital of Leipzig, and colleagues, explained that classification of LE can be difficult because it can be approached from 2 different angles. From a dermatological standpoint, the disease is typically assessed morphologically based on specific cutaneous lesions. However, a rheumatological approach to classification is focused on symptomatic factors, to gauge systemic involvement.

“To date, however, no classification has been established that takes both views equally into account,” Ziemer and colleagues wrote in their study, which was published in the Journal of the German Society of Dermatology.

In 2018, the European League Against Rheumatism and the American College of Rheumatology published new criteria (EULAR/ACR criteria) designed to combat this issue, but the investigators said that system and other new classifications are still problematic, in part because they consider the disease “exclusively from the perspective of systemic LE (SLE) positive for autoantibodies.”

Ziemer and colleagues believe improved classification is possible by assessing the dermatological and rheumatological manifestations of the disease separately, and then comparing them. The researchers devised an approach that considers the skin manifestations and final diagnosis separately. Using that system, the authors proposed they could more accurately classify LE into either limited-cutaneous LE, intermediate LE, and SLE.

To study their hypothesis, the investigators identified 76 patients with LE for whom complete clinical data, clinical photographs, and biopsies of cutaneous manifestations, and paraclinical findings were available. Their cases were retrospectively analyzed and re-classified using the 2-dimensional classification system. The investigators also evaluated the extent to which the patients’ LE skin manifestations corresponded with their corrected diagnosis.

The analysis suggested that patients were routinely classified in the least severe category, even when they had more severe, and even systemic, disease.

Initially, 81.6% of the patients in the study were diagnosed as having limited-cutaneous LE, and 18.4% were diagnosed with SLE. However, upon re-evaluation with the two-dimensional system, only 23.7% of patients were classified as limited-cutaneous LE. A plurality of patients (44.7%) were put in the intermediate category. The remaining one-third (31.6%) were classified with SLE.

“This finding demonstrates that the majority of LE patients have symptoms or clinical characteristics beyond the purely cutaneous manifestations and emphasizes the systemic character of the disease,” Ziemer and colleagues wrote.

The investigators said these data show that even the most recent criteria are still too oriented toward SLE, and insufficient when it comes to diagnosing patients whose disease cannot be considered systemic.

“While the EULAR/ACR classification from 2018, in particular, includes more forms of cutaneous manifestation, it remains unclear on which basis the selection was made and why some were included but others not,” they wrote.

The investigators concluded that skin manifestations alone are insufficient to correctly classify SLE. “A 2-dimensional approach can overcome the difficulties of classification, as skin-related morphological and symptomatic aspects can be considered separately,” they concluded.

Weldemann A, Ziepert M, Kreuz M, et al. Lupus erythematosus: correlation of clinical and histological findings and proposal for a modified disease classification. J Dtsch Dermatol Ges. Published online November 10, 2021. doi:10.1111/ddg.14548