Expert Perspective: Diagnosis and Treatment of Castleman Disease.

in Arthritis & rheumatology (Hoboken, N.J.) by Luke Y C Chen, Lu Zhang, David C Fajgenbaum

TLDR

  • Castleman disease is a challenging diagnostic and therapeutic issue for Rheumatologists, with various subtypes and clinical scenarios.
  • The study highlights the importance of distinguishing between unicentric and multicentric CD, and its three subtypes, and provides an overview of current treatment options.

Abstract

Castleman disease (CD) is a major diagnostic challenge for Rheumatologists. Unicentric CD (UCD) involves one enlarged lymph node region whereas multicentric CD (MCD) involves multiple enlarged lymph node regions. Both UCD and MCD may exhibit a wide range of symptoms that overlap with other immune-mediated conditions. MCD can be associated with excessive cytokine production due to a plasma cell neoplasm (MCD-POEMS) or uncontrolled human herpesvirus-8 infection (HHV-8 positive MCD), but over half of cases are idiopathic. Although they are all driven by excessive cytokines such as interleukin (IL)-6, patients with idiopathic MCD (iMCD) often present as a diagnostic mystery with heterogeneous symptomatology that can be classified into three subtypes. The three subtypes are: iMCD-TAFRO (thrombocytopenia, anasarca, fever, renal dysfunction/reticulin fibrosis, organomegaly), iMCD-IPL (idiopathic plasmacytic lymphadenopathy), and iMCD-NOS (not otherwise specified). Rapid onset cytokine storm with severe inflammation, anasarca, thrombocytopenia, and small volume lymphadenopathy, similar to hemophagocytic lymphohistiocytosis (HLH) or sepsis, are the hallmarks of iMCD-TAFRO. Patients with iMCD-IPL present with subacute or chronic lymphadenopathy, anemia of inflammation, andpolyclonal hypergammaglobulinemia, often with increased IgG4 in serum and lymph node tissue; these cases can be difficult to distinguish from IgG4-related disease and histiocyte disorders. Those who have iMCD not meeting criteria for TAFRO or IPL have iMCD-NOS, which often mimics indolent lymphoma or autoimmune conditions. Patients with autoimmune disease, lymphoma, and infections can Castleman-like changes in reactive lymph nodesand thus, histological findings must be combined with clinical and laboratory findings to accurately diagnose iMCD. Broadly speaking, treatments for Castleman disease can be considered in three categories: immunomodulators such as corticosteroids, cytokine inhibitors and sirolimus; anti-lymphoma therapies such as rituximab, cytotoxic chemotherapy and bruton's tyrosine kinase inhibitors, and anti-myeloma therapies such as thalidomide and bortezomib. The first-line therapy for all subtypes of iMCD is siltuximab, an IL-6 antagonist. Patients with refractory disease have numerous treatment options and consulting treatment guidelines as well as consultation with a center with expertise in Castleman disease are recommended.

Overview

  • The study focuses on the diagnosis and treatment of Castleman disease (CD), which is a major diagnostic challenge for Rheumatologists.
  • The study highlights the importance of distinguishing between unicentric CD (UCD) and multicentric CD (MCD) and their respective subtypes.
  • The primary objective of the study is to provide a comprehensive overview of the current understanding of CD and its management options.

Comparative Analysis & Findings

  • The study identifies three subtypes of idiopathic multicentric CD (iMCD): iMCD-TAFRO, iMCD-IPL, and iMCD-NOS, each with distinct clinical and laboratory features.
  • The study reveals that the hallmarks of iMCD-TAFRO include rapid onset cytokine storm, severe inflammation, anasarca, thrombocytopenia, and small volume lymphadenopathy, similar to hemophagocytic lymphohistiocytosis (HLH) or sepsis.
  • The study highlights the importance of combining histological, clinical, and laboratory findings to accurately diagnose iMCD and distinguish it from other conditions such as IgG4-related disease and histiocyte disorders.

Implications and Future Directions

  • The study's findings have significant implications for the diagnosis and management of patients with CD, emphasizing the importance of identifying the correct subtype and developing personalized treatment plans.
  • Future research directions include investigating novel therapeutic agents and combination therapy approaches for refractory disease, as well as exploring the role of precision medicine in CD treatment.
  • The study also underscores the need for increased awareness and education among healthcare providers about the complexities of CD diagnosis and management.
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