From the Guidelines
Castleman's disease is a rare lymphoproliferative disorder characterized by abnormal growth of lymph node tissue, also known as Angiofollicular lymph node hyperplasia, which can be treated with siltuximab, an anti-IL6 antibody, especially in HIV-negative, HHV-8 negative multicentric disease cases, as supported by its approval for this specific condition 1.
Definition and Forms
Castleman's disease comes in two main forms: unicentric (affecting a single lymph node region) and multicentric (affecting multiple lymph nodes throughout the body). The disease results from dysregulated production of interleukin-6 and other inflammatory cytokines, leading to lymph node enlargement, systemic inflammation, and in severe cases, multiple organ dysfunction.
Treatment Approaches
Treatment depends on the type of Castleman's disease. For unicentric Castleman's disease, surgical removal of the affected lymph node is typically curative. For multicentric Castleman's disease, treatment often includes rituximab, sometimes combined with chemotherapy agents. Siltuximab, an anti-IL6 antibody, is specifically approved for HIV-negative, HHV-8 negative multicentric disease, highlighting its role in managing this condition by targeting the interleukin-6 pathway, which is implicated in the disease's pathogenesis 1.
Key Considerations
Patients with Castleman's disease should be monitored for disease progression, infections, and development of lymphoma. The use of siltuximab in Castleman's disease is based on its mechanism of action, targeting IL-6, a key cytokine involved in the disease process, as discussed in the context of its potential use in managing immunotherapy-related toxicities 1.
From the Research
Definition and Classification of Castleman's Disease
- Castleman's disease (CD) is a group of rare and heterogeneous disorders with characteristic lymph node histopathological abnormalities 2, 3, 4, 5, 6.
- It can occur in a single lymph node station, referred to as unicentric CD (UCD), or involve multicentric lymphadenopathy and inflammatory symptoms, known as multicentric Castleman disease (MCD) 2, 3, 5, 6.
- MCD can be further divided into idiopathic MCD (iMCD), which includes thrombocytopenia, ascites, fibrosis, renal impairment, and organ enlargement (TAFRO) syndrome, and human herpesvirus-8 (HHV-8)-associated MCD 4, 5.
Clinical Presentation and Diagnosis
- The clinical presentation of CD can include symptoms such as swollen lymph nodes, fever, anemia, and systemic inflammation 5, 6.
- Diagnostic challenges arise due to the disease's rarity, and its symptoms overlap with other conditions 5.
- The diagnosis of CD is based on histopathological features and can be classified into different subtypes, including hyaline-vascular, plasma-cell, mixed type, hypervascular, and plasmablastic subtypes 6.
Treatment Approaches
- UCD generally responds favorably to the surgical removal of the affected lymph nodes 2, 3, 6.
- MCD often requires antiviral treatments, interleukin-6 (IL-6) inhibitors, and new biologic therapies 4, 5, 6.
- The anti-interleukin-6 monoclonal antibody siltuximab is a preferred treatment modality for MCD, with favorable symptomatic, laboratory, and radiologic outcomes and safety profiles 3, 4, 6.
- Recent advances in treatment, including innovative biologic agents and combination therapies, offer promising prospects for improving patient outcomes 5.