06/02/2025 Important insight for Castleman disease patients: Castleman disease (CD) is a major diagnostic challenge for rheumatologists. In this article the authors review and describe the wide range of symptoms exhibited by Castleman’s Disease (CD) patients and the overlap with other immune medicated conditions. The article reviews the different subtypes of CD, explaining the symptoms and the diagnostic criteria distinguishing each subtype. The treatment options for CD can be considered in three categories and are discussed. Patients with refractory disease have numerous treatment options and consulting treatment guidelines as well as consultation with a center with expertise in CD are recommended.
Summary: This open-access “Expert Perspectives on Clinical Challenges” article frames Castleman disease (CD) as a major diagnostic challenge for rheumatologists and walks through how to recognize and treat its subtypes. It distinguishes unicentric CD (UCD)—one enlarged lymph-node region—from multicentric CD (MCD), which involves multiple regions, noting that both can produce a wide range of symptoms overlapping with other immune-mediated conditions. MCD is driven by excessive cytokines (notably IL-6) and can stem from a plasma cell neoplasm (POEMS-associated) or uncontrolled HHV-8 infection (HHV-8–positive MCD), though more than half of cases are idiopathic (iMCD). The authors emphasize that iMCD is a diagnostic mystery with heterogeneous presentations and classify it into three subtypes: iMCD-TAFRO (thrombocytopenia, anasarca, fever, renal dysfunction/reticulin fibrosis, organomegaly—a rapid, severe cytokine storm resembling hemophagocytic lymphohistiocytosis or sepsis); iMCD-IPL (idiopathic plasmacytic lymphadenopathy, presenting more subacutely with anemia, polyclonal hypergammaglobulinemia, and elevated IgG4, sometimes mimicking IgG4-related disease); and iMCD-NOS (not otherwise specified, which can mimic indolent lymphoma or autoimmune disease). Because autoimmune conditions, lymphomas, and infections can cause Castleman-like reactive lymph-node changes, the authors stress that histology must be interpreted alongside clinical and laboratory findings. Treatments fall into three categories—immunomodulators (glucocorticoids, cytokine inhibitors, sirolimus), antilymphoma therapies (rituximab, cytotoxic chemotherapy, BTK inhibitors), and antimyeloma agents (thalidomide, bortezomib)—with the IL-6 antagonist siltuximab recommended as first-line therapy for all iMCD subtypes, and referral to guidelines and a CD-expert center advised for refractory disease.