Makindo Medical Notes

HHV-8 is the well-established cause of HHV-8-associated MCD, which accounts for approximately 50% of all cases of MCD.

About

• Castleman disease was originally described in a case published in 1954.
• A rare condition that affects the lymph nodes and related tissues.
• There are two main forms: unicentric CD (UCD) and multicentric CD (MCD).
• Also known as angiofollicular lymph node hyperplasia or benign giant lymph node hyperplasia.

Aetiology

• The exact cause of Castleman disease is currently unknown.
• Some patients have concurrent HIV and/or HHV-8 infection.
• In UCD, interleukin (IL)-6 plays a significant role; in MCD, both IL-6 and HHV-8 are implicated.
• Dysregulated and overproduced IL-6, especially in MCD, stimulates the production of acute-phase reactants in the liver and plasma cells.

Clinical Types

• Unicentric CD (UCD): A localized form, usually confined to a single set of lymph nodes.
• Multicentric CD (MCD): A systemic form that affects multiple lymph nodes and other tissues throughout the body.

Pathological Types

• Hyaline-Vascular Type: Comprises about 90% of cases. Characterized by germinal follicles with hyalinized vessels, surrounded by concentric layers of small lymphocytes and proliferative interfollicular vascular stroma.
• Plasma Cell Type: Features sparse follicular hyalinized vessels with dense sheets of plasma cells in interfollicular tissues and minimal vascular stroma.

Associated Conditions

• Large B-cell lymphomas
• POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, Skin changes)
• Follicular dendritic cell sarcomas
• Paraneoplastic pemphigus
• Kaposi sarcoma, especially with HHV-8-associated MCD
• Eruptive cherry hemangiomas or violaceous papules
• Lymphocytic interstitial pneumonitis

Clinical Presentation

• B symptoms: Fever, night sweats, and weight loss.
• UCD: Typically presents in the third or fourth decade, with a mean age of diagnosis at 34. Females are slightly more affected. Painless lymphadenopathy is common, often in the chest (30%), neck (23%), abdomen (20%), retroperitoneum (17%), and, less commonly, the axilla, groin, or pelvis. Some may exhibit B symptoms.
• MCD: Generally presents in the 50s, though younger in those with HIV/HHV-8. Slight male predominance. Findings include generalized lymphadenopathy, hepatosplenomegaly, fluid retention, gravitational oedema, pleural and pericardial effusions, ascites, and B symptoms.

Investigations

• FBC: May reveal anaemia. Elevated CRP and ESR; platelet count may be high or low.
• Hypergammaglobulinemia: Common finding.
• Hypoalbuminemia: Indicative of disease activity.
• U&E: Possible renal impairment.
• Cytokine Levels: Elevated IL-6 and IL-10.
• HIV and HHV-8 serology: Particularly relevant in MCD, where plasma levels of HHV-8 DNA correlate with symptoms and predict relapse rates.
• Imaging (CT/MRI): Can show enlarged lymph nodes, hepatosplenomegaly, and other systemic involvement.

Management

• Unicentric CD: Typically of the hyaline-vascular type and often curable with surgical resection. Radiation therapy is also an option with high response rates.
• Multicentric CD: Usually of the plasma cell type, associated with more complex systemic symptoms.
  • First-line Treatment: Rituximab monotherapy is the mainstay. For those with HHV-8, antiretroviral therapy (HAART) should be initiated.
  • Novel Therapies: Agents targeting IL-6 (e.g., Siltuximab, Tocilizumab) show promise. Siltuximab is FDA-approved for HIV-negative, HHV-8-negative MCD, effectively controlling IL-6–mediated symptoms.
  • Chemotherapy: Options include cytotoxic agents like oral etoposide, vinblastine, cyclophosphamide, cladribine, chlorambucil, and liposomal doxorubicin. Rituximab can be used for HIV-negative patients.
  • Anti-Inflammatory Therapy: Glucocorticoids, such as Prednisone (1 mg/kg daily), may be combined with rituximab until symptoms are controlled, then tapered off.
• Careful management is necessary to monitor and treat associated infections, malignancies, and other syndromes.

Algorithm

References

• Castleman's disease
• Castleman's disease Radiology