What is the treatment approach for Castleman disease in patients with Systemic Lupus Erythematosus (SLE)?

Castleman Disease and Its Association with SLE

Recognition and Diagnostic Approach

Castleman disease (CD) should be strongly considered in SLE patients with persistent lymphadenopathy, especially when accompanied by fever, splenomegaly, or inadequate response to standard SLE therapy. 1, 2

The clinical overlap between these conditions creates significant diagnostic challenges:

• CD can mimic SLE with fever, serositis, cytopenias, hypocomplementemia, and even positive autoantibodies including anti-dsDNA and anti-Sm, making differentiation extremely difficult 2, 3
• The two conditions may genuinely coexist rather than simply mimicking each other, though this remains incompletely understood pathophysiologically 1, 3
• Lymph node biopsy is essential when SLE patients have persistent lymphadenopathy or fail to respond appropriately to standard immunosuppressive therapy 1, 2

Key Clinical Red Flags Suggesting CD Rather Than Pure SLE:

• Negative or weakly positive ANA despite meeting SLE classification criteria 2
• Poor response to standard SLE treatments (glucocorticoids, hydroxychloroquine, immunosuppressants) 2
• Prominent sustained fever with marked constitutional symptoms 4
• Splenomegaly, pleural effusion, and ascites disproportionate to other SLE manifestations 4
• Renal biopsy showing proliferative glomerulonephritis with negative immunofluorescence 2

Treatment Strategy for Coexistent CD and SLE

For Unicentric Castleman Disease (UCD) with SLE:

Surgical resection of the solitary mass is the definitive treatment for UCD, with excellent prognosis regardless of coexistent SLE. 5, 4

• Complete surgical excision provides cure in UCD cases 5
• Following resection, continue standard SLE management with hydroxychloroquine and glucocorticoids as needed 1
• One pediatric case achieved remission within 3 months using hydroxychloroquine and steroids post-operatively 1

For Multicentric Castleman Disease (MCD) with SLE:

Systemic therapy targeting interleukin-6 with siltuximab is the preferred first-line treatment for MCD, even in patients with coexistent SLE. 5, 4

The treatment algorithm should proceed as follows:

• First-line: Siltuximab (anti-IL-6 monoclonal antibody) has demonstrated favorable symptomatic, laboratory, and radiologic outcomes with good safety profiles 4
• Second-line: Rituximab monotherapy remains an established option when siltuximab is unavailable or fails 5
• Third-line: Combination chemotherapy using CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) regimen for refractory cases 5, 2
• Concurrent SLE management: Continue hydroxychloroquine (not exceeding 5 mg/kg real body weight) as it reduces mortality and disease activity 6
• Glucocorticoid strategy: Use systemic steroids but rapidly taper to ≤7.5 mg/day prednisone equivalent once disease control is achieved 6

Critical Management Considerations:

• Monitor for infections vigilantly, as both SLE and CD treatments increase infection risk substantially 7, 6
• Screen for malignancies, particularly non-Hodgkin's lymphoma, which is associated with both conditions 7, 5
• Assess for HHV-8 and HIV status in all MCD cases, as this affects treatment selection 5
• Age ≥60 years and splenomegaly are independent poor prognostic factors in MCD requiring more aggressive monitoring 4

Treatment Response Monitoring:

• Overall survival in CD is approximately 90%, though progression-free survival is significantly poorer in MCD compared to UCD 4
• Clinical, laboratory, and radiologic response should be assessed regularly using validated SLE disease activity indices (SLEDAI, BILAG, or ECLAM) 7, 6
• Consider re-biopsy if clinical deterioration occurs despite appropriate therapy 1, 2

Common Pitfalls to Avoid:

• Never assume lymphadenopathy in SLE is purely reactive without tissue diagnosis, especially if disproportionate or persistent 1, 2
• Do not continue escalating standard SLE immunosuppression (azathioprine, mycophenolate) indefinitely without response—this suggests an alternative or additional diagnosis 2
• Avoid attributing all systemic symptoms to SLE activity when CD may be the primary driver requiring different therapeutic approaches 2, 3
• Do not delay lymph node biopsy in patients with negative autoantibodies who otherwise meet SLE criteria 2