From the Guidelines
Castleman disease, also known as Angiofollicular Lymph Node Hyperplasia, is a rare disorder characterized by abnormal growth of lymph nodes due to an overgrowth of cells in the lymphatic system, with treatment options including siltuximab, an anti-IL6 antibody approved for the treatment of this condition 1.
Definition and Forms
Castleman disease comes in two main forms: unicentric (affecting a single lymph node region) and multicentric (affecting multiple lymph node regions). The unicentric form is typically benign and can often be cured with surgical removal of the affected lymph node. Multicentric Castleman disease is more serious, often associated with HIV infection or human herpesvirus 8, and requires systemic treatment.
Symptoms and Treatment
Symptoms may include enlarged lymph nodes, fever, night sweats, fatigue, weight loss, and sometimes organ dysfunction. Treatment depends on the type and may include surgery, rituximab (a monoclonal antibody), siltuximab (an IL-6 inhibitor), steroids like prednisone, or chemotherapy regimens.
- Key treatment options:
- Siltuximab: an anti-IL6 antibody approved for the treatment of Castleman’s disease 1
- Rituximab: a monoclonal antibody
- Steroids: like prednisone
- Chemotherapy regimens
Pathophysiology
The disease results from dysregulation of the immune system, particularly involving interleukin-6 (IL-6), which promotes inflammation and cell growth. Early diagnosis and appropriate treatment are essential for managing this condition, especially for the multicentric form which can be life-threatening if left untreated. The use of siltuximab, as mentioned in the study 1, highlights the importance of targeting the IL-6 pathway in the treatment of Castleman disease.
From the Research
Definition and Classification of Castleman Disease
- Castleman disease, also known as angiofollicular lymph node hyperplasia, is a rare lymphoproliferative disorder characterized by enlarged hyperplastic lymph nodes with striking vascular proliferations 2, 3.
- It is categorized as being either localized (unicentric) or disseminated (multicentric) and further subdivided into hyaline-vascular, plasma cell, or mixed histopathological patterns 2, 3.
Clinical Features and Treatment
- Unicentric Castleman disease is typically localized and symptoms are minimal, often treated locally with surgical excision, which can be curative 2, 4, 5.
- Multicentric Castleman disease is systemic and clinically characterized by generalized lymphadenopathy, splenomegaly, anemia, and systemic inflammatory symptoms, requiring systemic therapies 2, 3.
- Treatment strategies for multicentric Castleman disease include steroids, combination chemotherapy, and novel therapies, although these are still in an experimental phase 2.
Pathogenesis and Associated Conditions
- The pathogenesis of Castleman disease is not completely understood, but the role of interleukin (IL)-6 in unicentric disease and the roles of IL-6 and human herpes virus-8 in multicentric disease are well defined 3.
- Castleman disease can be associated with several malignant diseases, including lymphomas, POEMS syndrome, follicular dendritic cell sarcomas, paraneoplastic pemphigus, Kaposi sarcoma, and amyloidosis 3.