Perspective highlights diagnostic overlap between idiopathic multicentric Castleman disease and systemic lupus erythematosus

Castleman disease (CD) is a rare lymphoproliferative disorder with heterogeneous clinical manifestations, particularly in its idiopathic multicentric form (iMCD), which is driven by cytokine dysregulation rather than classical autoimmunity. Owing to overlapping features such as fever, lymphadenopathy, cytopenias, renal involvement, and elevated inflammatory markers, iMCD may closely mimic systemic lupus erythematosus (SLE). This resemblance is further complicated by the presence of autoantibodies in a subset of iMCD patients, increasing the risk of misclassification and delayed diagnosis. In this Perspective, we highlight key clinical scenarios in which CD presents as a lupus-like syndrome, including cases that initially fulfill SLE classification criteria but fail to respond to conventional immunosuppressive therapy. We emphasize the limitations of serologic testing in distinguishing these entities and underscore the central role of lymph node histopathology in establishing the correct diagnosis. Recognizing Castleman disease as an important mimic of SLE has critical therapeutic implications, as iMCD requires cytokine-directed treatment rather than immune suppression alone. These observations also suggest that CD and SLE may share a cytokine-driven inflammatory spectrum in selected patients; however, distinguishing between them remains essential because their therapeutic strategies differ fundamentally. Increased awareness of this diagnostic overlap may help clinicians avoid inappropriate treatment strategies and improve outcomes in patients presenting with atypical or refractory lupus-like disease.