Makindo Medical Notes

🦠 HHV-8 is the well-established cause of HHV-8-associated Multicentric Castleman Disease (MCD), accounting for ~50% of MCD cases.

📖 About

• Castleman disease first described in 1954.
• A rare lymphoproliferative disorder affecting lymph nodes and surrounding tissues.
• Two main forms: Unicentric CD (UCD) and Multicentric CD (MCD).
• Also called angiofollicular lymph node hyperplasia or benign giant lymph node hyperplasia.

🧬 Aetiology

• Exact cause unknown.
• Some patients have HIV and/or HHV-8 infection.
• UCD ➝ IL-6 driven. MCD ➝ IL-6 + HHV-8 involvement.
• IL-6 overproduction drives inflammation and acute-phase response.

📌 Clinical Types

• Unicentric CD (UCD): Localised to one lymph node region.
• Multicentric CD (MCD): Systemic, affecting multiple lymph nodes + other organs.

🔬 Pathological Types

• Hyaline-Vascular Type: ~90% cases; follicles with hyalinised vessels + concentric lymphocytes + vascular stroma.
• Plasma Cell Type: Dense sheets of plasma cells in interfollicular tissue, minimal vascular stroma.

🧩 Associated Conditions

• Large B-cell lymphoma
• POEMS syndrome
• Follicular dendritic cell sarcoma
• Paraneoplastic pemphigus
• Kaposi sarcoma (esp. HHV-8 MCD)
• Eruptive cherry haemangiomas / violaceous papules
• Lymphocytic interstitial pneumonitis

🩺 Clinical Presentation

• B symptoms: Fever 🌡️, night sweats 😓, weight loss ⚖️.
• UCD: Dx mean age ~34, F>M. Painless lymphadenopathy in chest (30%), neck (23%), abdomen (20%), retroperitoneum (17%). May have B symptoms.
• MCD: Age ~50s (younger in HIV/HHV-8), M>F. Findings:
  • Generalised lymphadenopathy
  • Hepatosplenomegaly
  • Fluid retention ➝ oedema, effusions, ascites
  • B symptoms

🧪 Investigations

• Bloods: Anaemia, ↑ CRP/ESR, thrombocytosis or thrombocytopenia.
• Biochemistry: Hypergammaglobulinaemia, hypoalbuminaemia, renal impairment.
• Cytokines: ↑ IL-6, IL-10.
• Serology: HIV + HHV-8 testing; HHV-8 DNA load correlates with symptoms + relapse.
• Imaging (CT/MRI): Enlarged nodes, hepatosplenomegaly, systemic spread.

💊 Management

• Unicentric CD:
  • Usually hyaline-vascular type.
  • Curable with surgical resection.
  • Radiotherapy is an alternative with high response rates.
• Multicentric CD:
  • First-line: Rituximab (esp. HHV-8+). Add HAART in HIV cases.
  • IL-6 Blockade: Siltuximab (FDA-approved for HIV-/HHV-8- MCD), Tocilizumab also used.
  • Cytotoxic Chemotherapy: Etoposide, vinblastine, cyclophosphamide, cladribine, chlorambucil, liposomal doxorubicin.
  • Immunotherapy: Rituximab + steroids (Prednisone 1 mg/kg) until controlled, then taper.
  • Supportive Care: Manage infections, malignancies, paraneoplastic syndromes.

📊 Algorithm

📚 References

• Castleman's Disease – Moffitt
• Radiology – Castleman’s Disease