Updates on the Evaluation of Lupus Arthritis

Lupus arthritis is the most common manifestation of systemic lupus erythematosus (SLE), affecting up to 95% of patients. Clinical presentations range from inflammatory arthralgia and non-deforming non-erosive (NDNE) synovitis to Jaccoud arthropathy and erosive arthritis, reflecting substantial clinical heterogeneity. Despite its high prevalence, widely used outcome measures lack the granularity to distinguish between these phenotypes or accurately quantify disease severity. This narrative review integrates clinical phenotypes, serologic biomarkers, imaging advances, and emerging therapies to provide a framework for evaluating lupus arthritis. Besides distinct clinical phenotypes, we propose a conceptual hypothesis-generating model describing the evolution of lupus arthritis. In an early, preclinical stage, genetically predisposed individuals may develop pathogenic autoantibodies and alterations in the gut microbiome that can lead to increased inflammation within the synovium. The intermediate stage is characterized by progressive leukocyte accumulation within the joint space, leading to clinical symptoms and early abnormalities on imaging including joint effusions, synovitis, and tenosynovitis. In the late stage, persistent inflammation results in clinically evident joint damage, including synovial hypertrophy, joint capsular swelling, and bone erosions. Biomarkers such as anti-citrullinated protein antibodies (ACPAs), anti-carbamylated protein (anti-carP) antibodies, interleukin (IL)-6, IL-17, and metalloproteinases may help identify patients at risk for erosive or deforming disease and those prone to rapid progression. Advances in imaging technologies including musculoskeletal ultrasound (MSK-US), MRI, and optical tomography may enable earlier detection before clinical manifestations or physical exam findings, creating opportunities for earlier intervention. Therapeutically, hydroxychloroquine (HCQ) remains the foundation of treatment. Belimumab and anifrolumab are US Food and Drug Administration (FDA)-approved biologics now recommended as standard of care for persistent disease, alongside conventional immunosuppressants such as methotrexate, mycophenolate, or azathioprine when indicated. Additional targeted therapies including obinutuzumab and Janus kinase (JAK) inhibitors are closely following behind. Chimeric antigen receptor T cell (CAR-T) represents a promising approach that may transform the future management of SLE.