Clinical Pearls & Morning Reports

Posted by Carla Rothaus

Published May 25, 2022


What is the recommended initial therapy for idiopathic multicentric Castleman’s disease?

Castleman’s disease describes a group of rare and heterogeneous polyclonal lymphoproliferative disorders that are associated with a spectrum of characteristic histopathological features. Read the NEJM Case Records of the Massachusetts General Hospital here.

Clinical Pearls

Q: What are some of the features of hemophagocytic lymphohistiocytosis (HLH)?

A: A constellation of fevers, splenomegaly, cytopenias, and elevated levels of inflammatory markers is characteristic of HLH, which comprises a group of rare disorders of immune hyperactivation triggered by infection, cancer, or autoimmune diseases. A normal fibrinogen level and a ferritin level of less than 1000 μg per liter would be uncommon in a patient with HLH. Evidence of hemophagocytosis in bone marrow and decreased natural-killer-cell activity would support a diagnosis of HLH; a mildly elevated level of soluble interleukin-2 receptor, which reflects T-cell activation, is highly sensitive but less specific for HLH.

Q: Name some of the conditions associated with multicentric Castleman’s disease (MCD).

A: MCD involves multicentric lymphadenopathy, constitutional symptoms, cytopenias, anasarca, and organ dysfunction due to a cytokine storm, often driven by interleukin-6. MCD can result from uncontrolled human herpesvirus 8 (HHV-8) infection in persons with HIV infection or an immunocompromised state (HHV-8–associated MCD), can be due to cytokine production by monoclonal plasma cells (POEMS [polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes]–associated MCD), or can have an unknown or uncertain cause (idiopathic MCD).

Morning Report Questions

Q: What are some of the settings in which a diagnosis of idiopathic MCD should be considered?

A: Idiopathic MCD is a challenging diagnosis that can progress rapidly to a deadly cytokine storm. Given the diagnostic urgency, idiopathic MCD should be in the differential diagnosis any time an inflammatory syndrome and lymphadenopathy have developed concurrently or any time HLH is considered.

Q: What is the recommended initial therapy for idiopathic MCD?

A: Siltuximab, a monoclonal antibody that binds to interleukin-6, has been approved by the Food and Drug Administration for the treatment of patients with idiopathic MCD, and current guidelines recommend siltuximab as initial therapy. Alternatively, combination cytotoxic chemotherapy is also active against this disease and has been associated with frequent objective responses among patients with idiopathic MCD in retrospective series.

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