Castleman's disease
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
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Overview
Castleman's disease is a rare disorder characterized by non-cancerous growths (tumors) that may develop in the lymph node tissue throughout the body. It involves hyperproliferation of certain B cells that often produce cytokines.
There are several variants of Castleman's disease. About 50% of Multicentric Castleman's disease (MCD) is caused by Kaposi's sarcoma-associated herpesvirus (KSHV), a gammaherpesvirus that is also the cause of Kaposi's sarcoma and primary effusion lymphoma, while the remainder of MCD are of unknown cause. The form of MCD most closely associated with KSHV is the plasmacytic form of Castleman's disease while another pathologic form, the hyaline-vascular form, is generally negative for this virus. In all cases, Castleman's disease is likely due to hypersecretion of the cytokine IL-6. In KSHV positive tumors, this is most likely due to expression of the a virus-encoded cytokine, vIL-6, while KSHV negative tumors appear to be the result of over secretion of human IL-6.
Symptoms
The most common 'B Symptoms' of MCD are high fevers, anemia, weight loss, loss of appetite, and low white blood cell counts, which may to be due to the overproduction of interleukin 6. Symptomatically, therefore, MCD can be difficult to diagnose and even in the case of a lymph-node biopsy a conclusive diagnosis remains problematic.
Treatment
There is no standard therapy for Castleman's disease at the moment; prior to 1996 MCD has carried a poor prognosis of about 2 years, due to autoimmune hemolytic anemia, non-Hodgkin's lymphoma which may arise as a result of proliferation of infected cells. The timing of diagnosis, with particular attention to the difficulty of determining the cause of B symptoms without a CT scan and lymph node biopsy, may impact significantly on the prognosis and risk of death. Left untreated, MCD usually gets worse and becomes increasingly difficult and unresponsive to current treatment regimens. Recent work with HIV-positive patients with KSHV-related MCD suggests that treatment with the antiherpesvirus drug ganciclovir or the antiCD20 B cell monoclonal antibody, rituximab, may markedly improve outcome. These drugs target and kill B cells using the CD20 marker of a patient's antibody. Since B cells are required for the production of white blood cells, the body's immune response is weakened whilst on treatment and the risk of further viral or bacterial infection is increased. Due to the uncommon nature of the condition there are not many large scale research studies from which standardized approaches to therapy may be drawn, and the extant case studies of individuals or small cohorts should be read with caution. As with many diseases, the patient's age, physical state and previous medical history with respect to infections may impact on the disease progression and outcome.
Prior to 1996 and before HAART triple therapy was introduced for HIV positive patients, the prognosis of Kaposi's Sarcoma was about 18 months. Today, the prognosis for Kaposi's is generally very good and people with HIV KS can expect to have a successful outcome with current treatment regimens. This indicates that although the prognosis for MCD is two to three years, it is still retrospectively better than Kaposi's was historically, which is now a treatable and manageable condition.
References
- Aoki Y, Yarchoan R, Wyvill K, Okamoto S, Little RF, Tosato G. Detection of viral interleukin-6 in Kaposi sarcoma-associated herpesvirus-linked disorders. Blood 2001;97(7):2173-6.
- Yarchoan R, Little RF. Immunosuppression-related malignancies. In: DeVita Jr. VT, Hellman S, Rosenberg SA, eds. Cancer, Principles and Practice of Oncology 6th Edition. Philadelphia: Lippincott Williams and Wilkins; 2001:2575-97.