How to manage a patient with Castleman disease and a history of Systemic Lupus Erythematosus (SLE)?

Managing Castleman Disease in Patients with Systemic Lupus Erythematosus

Critical Recognition: These Are Distinct Entities Requiring Different Treatment Paradigms

The coexistence of Castleman disease (CD) and SLE represents two separate pathological processes that require simultaneous but distinct therapeutic approaches—CD requires either surgical excision (if unicentric) or IL-6 targeted therapy with siltuximab (if multicentric), while SLE requires standard immunosuppressive management with hydroxychloroquine, glucocorticoids, and steroid-sparing agents. 1, 2

Step 1: Confirm Both Diagnoses Through Tissue Biopsy

• Lymph node biopsy is mandatory to establish the diagnosis of CD, as clinical and laboratory features overlap substantially with SLE and can lead to misdiagnosis 2, 3, 4
• The histopathological examination will reveal either hyaline-vascular variant (most common in unicentric CD, ~75% of cases) or plasma cell variant 5
• Do not rely solely on SLE classification criteria or autoantibodies, as CD can mimic SLE with fever, lymphadenopathy, cytopenias, hypocomplementemia, and even positive autoantibodies 3, 4
• PET/CT imaging helps differentiate unicentric from multicentric disease and guides surgical planning 4

Step 2: Determine CD Subtype and Treat Accordingly

For Unicentric Castleman Disease:

• Surgical excision is curative and should be performed as definitive treatment 5
• After surgical removal, continue standard SLE management with hydroxychloroquine (≤5 mg/kg real body weight) and glucocorticoids 2, 6
• Monitor for disease remission at 3-month intervals 2

For Multicentric Castleman Disease (MCD):

• Siltuximab (anti-IL-6 antibody) 11 mg/kg IV every 3 weeks is the FDA-approved treatment for HIV-negative and HHV-8-negative MCD 1
• Siltuximab specifically targets IL-6, the key cytokine driving MCD pathogenesis, and is superior to tocilizumab for this indication as it directly binds IL-6 rather than the receptor 7, 1
• Perform hematology laboratory tests prior to each siltuximab dose for the first 12 months, then every 3 dosing cycles thereafter 1
• Treatment criteria before each dose: absolute neutrophil count ≥1.0 × 10⁹/L, platelet count ≥50 × 10⁹/L (after first dose), hemoglobin <17 g/dL 1

Step 3: Manage SLE Concurrently with Standard Therapy

Foundation Therapy:

• Hydroxychloroquine at ≤5 mg/kg real body weight is mandatory for all SLE patients unless contraindicated 6, 8
• Ophthalmological screening at baseline, after 5 years, then yearly thereafter 6, 8
• Glucocorticoids should be minimized to <7.5 mg/day prednisone equivalent for chronic maintenance 6, 8

Immunosuppressive Selection Based on SLE Manifestations:

• For skin and joint manifestations: methotrexate 6
• For maintenance therapy (especially in women of childbearing potential): azathioprine 6, 2, 4
• For renal or non-renal manifestations: mycophenolate mofetil 6
• For severe organ-threatening disease: cyclophosphamide 6

Step 4: Monitor for Treatment Response and Complications

• Assess SLE disease activity at each visit using validated indices (SLEDAI) 7, 8
• Monitor anti-dsDNA, C3, C4, complete blood count, creatinine, proteinuria, and urine sediment 7, 8
• Screen for malignancies, particularly non-Hodgkin's lymphoma, as SLE patients have increased risk 7, 8
• Evaluate for infections given dual immunosuppression from both SLE treatment and potential siltuximab therapy 7, 1

Critical Pitfalls to Avoid

• Do not treat presumed SLE with standard immunosuppression alone if lymphadenopathy is present—always obtain tissue diagnosis to exclude CD, as the treatment paradigms differ fundamentally 2, 3, 4
• Do not use tocilizumab instead of siltuximab for MCD, as siltuximab is the FDA-approved agent with proven efficacy for this specific indication 1
• Do not delay surgical excision if unicentric CD is confirmed, as this is curative and prevents progression 5
• Do not attribute poor response to SLE therapy as treatment failure without reconsidering the diagnosis—CD can masquerade as refractory SLE 3, 4
• Do not use mycophenolate mofetil, cyclophosphamide, or methotrexate in pregnant patients; switch to azathioprine, hydroxychloroquine, and prednisolone 7, 6

Expected Outcomes

• Unicentric CD: Complete remission expected after surgical excision 2, 5
• Multicentric CD: Disease control with siltuximab, requiring ongoing therapy 1
• SLE: Aim for remission or low disease activity with glucocorticoid dose <7.5 mg/day 6, 8
• Combined remission achievable at 3-6 months with appropriate dual management 2, 4