ACR Convergence 2024—Arthritis symptoms related to lupus are a bit of a trouble spot for clinicians, with limited data to guide treatment and overlap with other conditions, experts said in a session at ACR Convergence.
Dr. Askanase
Lupus arthritis (LA) is present in 95% of patients with lupus, is the main cause of work-related disability and is a main driver for patients to enroll in clinical trials. Nonetheless, it is a difficult problem for clinicians to get their arms around, said Anca Askanase, MD, MPH, director of the Columbia University Lupus Center.
A meta-analysis of magnetic resonance imaging (MRI) studies and hand arthritis included eight studies and found not only manifestations such as synovitis tenosynovitis, but also “some slightly unexpected features,” such as capsular swelling and bone cysts.
“There’s a wide spectrum of abnormalities on ultrasound and MRI of people with lupus and hand arthritis,” she said.
Other work has found that subclinical synovitis on ultrasound could impact progression.1
Rheumatology researchers and engineers at Columbia are working on glove-like devices that use frequency domain optical imaging (FDOI) to help identify lupus arthritis. Near-infrared light is passed through tissues, and changes in optical properties related to physiologic changes can help with diagnosis. Researchers have identified three features of SLE joints, and the ultimate goal is to develop an actual glove for simple diagnosis.2
Work is ongoing, she said, “to fully understand if we can actually measure lupus arthritis with this new device.”
Lupus Arthritis Research Continues
Dr. Malmstroem
Vivianne Malmstrom, PhD, professor of medicine and an immunologist specializing in rheumatic diseases at the Karolinska Institute, said studies comparing lupus arthritis to rheumatoid arthritis and other rheumatic conditions have found some differences, but also quite a bit of overlap that can make it a bit vexing to assess.
In a study of about 900 patients, researchers at her center found that while ACPA-positive, rheumatoid factor-positive RA patients had a distinct HLA genetics profile not seen in seronegative RA, and that lupus patients could be subdivided into subgroups based on their autoantibody makeup and on HLA genetics, lupus arthritis patients were not easily distinguished.3
“Even though lupus arthritis was very much a part of this big analysis, the lupus arthritis group does not form its own subgroup,” Dr. Malmstrom said.
She said the “old dogma” held that lupus arthritis was not particularly erosive, but that perception has changed.
“Better imaging is showing that lupus arthritis can be erosive,” she said. What is more, she said, arthritis, tendonitis and tenosynovitis in lupus have probably tended to be underestimated by traditional clinical assessments.
“There’s so much excitement now with all this new imaging, new ways of studying patient material,” she said.
In a study of samples from a synovial fluid (SF) biorepository in Stockholm—with patients having a wide range of organ involvement and autoantibodies representative of lupus at large—researchers at her center tried to get a handle on the features that can distinguish lupus arthritis in this fluid.4
Among the observations were that IL6 is enriched in the SF compared to serum, with some patients having high values of IL17A and IL10 in the SF, while IL4 and IL2 were higher in the circulation. They also found that B cells comprised less than 1% of the mononuclear cells, “so it doesn’t seem like in synovial fluid that B cells are the main driver of the arthritis that we see.”
In their T cell analysis, researchers found that CCR6, a chemokine associated with TH17, was prominent, but this was also seen in spondyloarthritis and RA. Interferon gamma was most abundantly produced, Dr. Malmstrom said.
“There are many similarities and differences, and there are many things that we do not yet know about lupus arthritis,” she said.
Knowledge Gaps
Dr. Kalunian
Kenneth Kalunian, MD, the Wolfe Family Director of the University of California, San Diego Lupus Center of Excellence, noted how literature reviews have repeatedly identified knowledge gaps when it comes to how to best treat lupus arthritis.
The pathogenesis of LA has come into sharper focus but work remains to be done, and it’s still not clear on how it is best diagnosed.
“We really don’t know what the distribution of lupus arthritis is,” he said. “We really don’t know how to define treatment success.”
Lupus Arthritis Treatment
A report from a 2022 symposium suggested that the treatment choice requires the consideration of the clinical phenotypes, each with a different pathogenesis. They identified a non-deforming, non-erosive form with a type 1 interferon signature, a deforming arthritis marked by MMP3 and MMP12 enzymes, and a rheumatoid-like form marked by rheumatoid factor, ACPA, and anti-CarP antibodies.5
Nonetheless, with these and other guidelines, including the EULAR guidelines, questions remain about whether there are enough data to support these suggestions.
Analysis of belimumab data in lupus has found that patients with arthritis at baseline seem to have improved on the drug—a significant effect was seen in as little as 8 weeks, with 55.8% of belimumab patients having sustained resolution of symptoms compared to 47.8% of placebo patients, which Dr. Kalunian called “not a huge difference but a suggestion that something’s there.”6
An analysis of anifrolumab data done with his colleague, Dr. Rashmi Dhital, formerly a fellow at his center and now on the faculty at Vanderbilt University, found improvement for anifrolumab versus placebo among those with a swollen joint count of 2 at baseline, but no difference was seen with higher swollen joint counts until the count was more than 10. Dr. Kalunian said it wasn’t clear what to make of the data.
Improvements with the treatment were seen with smaller joints, but not with larger joints, the analysis also found.
Thomas Collins is a freelance medical writer based in Florida.
References
- Mahmoud K, Zayat A, Vital EM, et al. Musculoskeletal manifestations of systemic lupus erythematosus. Curr Opin Rheumatol. 2017 Sep;29(5):486–492.
- Marone A, Tang W, Kim Y, et al. Evaluation of SLE arthritis using frequency domain optical imaging. Lupus Sci Med. 2021 Aug 29;8(1):e000495.
- Diaz-Gallo L-M, Oke V, Lundstrom E, et al. Four systemic lupus erythematosus subgroups, defined by autoantibodies status, differ regarding HLA-DRB1 genotype associations and immunological and clinical manifestations. ACR Open Rheumatol. 2022 Jan;4(1):27–39.
- Sippl N, Faustini F, Ronnelid J, et al. Arthritis in systemic lupus erythematosus is characterized by local IL-17A and IL-6 expression in synovial fluid. Clin Exp Immunol. 2021 Jul;205(1):44–52.
- Ceccarelli F, Govoni M, Piga M, et al. Arthritis in systemic lupus erythematosus: From 2022 International GISEA/OEG Symposium. J Clin Med. 2022 Oct 12;11(20):6016.
- Leuchten N, Parodis I, Brinks R, Aringer M. Belimumab induces early and sustained resolution of lupus thrombocytopenia and lupus arthritis [abstract]. Arthritis Rheumatol. 2024;76(suppl 9).
