Abstract
Rhupus syndrome is a rare overlap disorder characterized by the co-occurrence of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Although its pathogenesis remains incompletely elucidated, associations with *HLA-DRβ1*0405*, sex hormone fluctuations, immune dysregulation, and environmental triggers have been proposed; the estimated incidence ranges from 0.01% to 0.2% among arthritis patients. We report two middle-aged female patients (52y and 78y) fulfilling both 2010 ACR/EULAR RA criteria and 2019 ACR/EULAR SLE, complicated by hypertension and hyperglycemia. Metabolic comorbidities constrained immunosuppressant use. Case 1 responded to methotrexate + tofacitinib with antihypertensive/lipid-lowering agents. Case 2 required total knee arthroplasty (TKA) after failed medical therapy, achieving significant pain relief; perioperative glycemic optimization was critical. Rhupus diagnosis mandates dual RA/SLE criteria; antinuclear antibody (ANA) screening is essential for arthritis patients to identify overlap syndromes. Aggressive metabolic control optimizes therapeutic safety. AI-enhanced imaging (e.g. erosion/synovitis detection) holds diagnostic promise.