What is the medical management of Castleman's disease?

Medical Management of Castleman's Disease

Rituximab is the recommended first-line therapy for HHV-8-associated multicentric Castleman disease (HHV-8-MCD), while anti-IL-6 therapy with siltuximab or tocilizumab is preferred for idiopathic multicentric Castleman disease (iMCD). 1, 2

Classification of Castleman's Disease

• Castleman's disease is classified into unicentric (UCD) and multicentric (MCD) forms based on the extent of lymph node involvement 3
• MCD is further divided into:
  • HHV-8-associated MCD (HHV-8-MCD) - commonly seen in HIV-positive patients 1
  • Idiopathic MCD (iMCD) - without identifiable HHV-8 infection 2
• Histopathological variants include hyaline vascular, plasma cell, and mixed types 3, 4

Diagnostic Approach

• Diagnosis requires lymph node biopsy with characteristic histopathological findings 3
• Laboratory evaluation should include:
  • Complete blood count with differential (anemia, thrombocytosis) 1
  • Inflammatory markers (ESR, CRP, IL-6 levels) 2
  • HHV-8 testing (serology, viral load) 1
  • HIV testing 1
• Imaging studies:
  • CT or FDG-PET/CT to assess extent of disease 1
  • Echocardiography to evaluate for pericardial effusion in HHV-8-MCD 1

Treatment of HHV-8-associated MCD

First-line therapy:

• Rituximab monotherapy is the recommended first-line treatment 1
• For severe cases with cytokine storm or hemophagocytic syndrome, add etoposide to rituximab 1
• When Kaposi sarcoma is present at MCD diagnosis, combine rituximab with cytotoxic chemotherapy (etoposide or liposomal doxorubicin) 1
• Antiretroviral therapy (ART) should always be administered in HIV-positive patients 1

Management of relapsed/refractory HHV-8-MCD:

• Multiple rechallenges with rituximab-based immunochemotherapy are effective 1
• More aggressive chemotherapy regimens (e.g., CHOP) can be considered in rituximab-refractory disease 1
• Regular monitoring of HHV-8 viral load, CRP, IL-6, and IL-10 levels is recommended 1

Treatment of Idiopathic MCD (iMCD)

First-line therapy:

• Anti-IL-6 therapy with siltuximab (or tocilizumab if siltuximab unavailable) with or without corticosteroids 2
• For severe cases, adjuvant combination chemotherapy may be added 2

Management of relapsed/refractory iMCD:

• Consider combination therapy with tocilizumab, lenalidomide, and glucocorticoids 5
• For aggressive disease, high-dose chemotherapy with autologous stem cell transplantation may be considered 6
• Triple therapy with corticosteroids, rituximab, and cyclophosphamide for severe inflammation or inadequate response to IL-6 blockade 7

Treatment of Unicentric Castleman's Disease (UCD)

• Complete surgical excision is curative for unicentric disease 3, 4
• For unresectable UCD, consider partial resection or radiation therapy 4

Follow-up and Monitoring

• Clinical follow-up every 3-6 months is recommended 1
• Monitor for:
  • Disease relapse (patients should seek medical attention if symptoms recur) 1
  • Development of NHL, particularly HHV-8-associated NHL (PEL, DLBCL) 1
  • Reactivation or progression of concomitant Kaposi sarcoma with rituximab treatment 1

Prognosis

• UCD has excellent prognosis with complete surgical resection 4
• MCD has poorer prognosis, particularly plasma cell variant 4
• Rituximab treatment reduces NHL incidence but risk remains high 1
• Patients should be educated about risk of relapse and need for prompt medical attention if symptoms recur 1

Special Considerations

• Splenectomy may be considered in cases with severe refractory anemia and thrombocytopenia 1
• Antivirals, immunomodulators, and IL-6-blocking agents have limited value in HHV-8-MCD 1
• POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M protein, skin changes) may be associated with Castleman's disease and requires specific diagnostic workup 8