The prevalence and clinical significance of enthesitis in SLE make an argument for the consideration of enthesitis as a musculoskeletal manifestation of SLE.

“In up to 95% of patients with systemic lupus erythematosus (SLE), musculoskeletal manifestations are observed, with joint pain commonly occurring as the initial symptom of the disease,” explains Giacomo Emmi, MD, PhD.  He adds that while joint inflammation is the most frequent finding in patients with SLE, all parts of the musculoskeletal system may potentially be involved.

“In SLE, musculoskeletal disease is associated with the development of disability and has a significantly negative influence on patients’ QOL,” says Dr. Emmi. “However, entheseal involvement is a frequently overlooked feature of SLE, and a characterization of patients with enthesitis is missing from clinical practice and trials. Epidemiological data about the incidence of entheseal involvement in SLE are lacking, and the clinical features of patients with SLE with enthesitis have not been described in the real-world setting.”

For a paper published in Rheumatology, Dr. Emmi and colleagues conducted a retrospective analysis to investigate the prevalence of  ultrasound (US)-confirmed enthesitis among 400 unselected patients with SLE attending the Lupus Unit of the Careggi University Hospital in Florence, Italy. The study team focused on possible associations of enthesitis with clinical and serological SLE features. Clinical, imaging, and therapeutic data were collected from medical charts. Laboratory and clinical features of patients with US-proven enthesitis were compared with those of SLE controls with tender and/or swollen joints with no US evidence of enthesitis.

Patients with Enthesitis Less Likely Develop Renal Involvement

In total, 106 patients underwent an articular US examination; 71 patients without US enthesitis served as controls. Evidence of enthesitis was found in 31 (29.2%) of the 106 patients. Compared with controls, patients with enthesitis were less likely to experience renal involvement (22.6% vs 46.5%; P=0.028) and more likely to experience failed B-cell depletion (75.0% vs 0%) throughout a median follow-up of 10.0 (interquartile range [IQR], 8.3-23.3) years for patients and 12.4 (IQR 7.2-13.3) years for controls.

“Physicians, particularly rheumatologists, should be aware that enthesitis can be found in up to one-third of patients with SLE who present with tender and/or swollen joints,” Dr. Emmi says. “Enthesitis in SLE could be the hallmark of a distinct disease phenotype with less renal involvement, more arthritis, and low response to anti-CD 20 therapy, potentially requiring a targeted treatment. Additionally, enthesitis might be considered as an outcome measure for monitoring musculoskeletal disease in SLE.”

Enthesitis Should Be Regarded as a Musculoskeletal Manifestation of SLE

Dr. Emmi and colleagues emphasized that a key takeaway message from their research is that, theoretically, all regions of the musculoskeletal system can be affected by enthesitis, and that clinicians who treat patients with SLE should take notice of all tender and/or swollen joints to assess the presence of enthesitis (Table).

“The considerable prevalence and clinical significance of enthesitis in SLE make an argument for the consideration of enthesitis as a musculoskeletal manifestation of SLE similar to synovitis and tenosynovitis,” Dr. Emmi notes. “Therefore, research efforts are needed to characterize the pathogenetic mechanisms sustaining enthesitis in SLE, and to investigate the possible potential of new targeted therapies (such as IL12/23 and TYK2) in a clinical setting.”