What Causes Castleman Disease?

We do not know exactly what causes Castleman disease (CD). The main feature of CD is an overgrowth of lymphocytes (immune cells) called B cells. The cause of this overgrowth is not known for sure, but it seems to be related to problems with the way a person’s immune system is working. Many people with CD have abnormally high blood levels of certain substances made by immune system cells.

For example, in the multicentric form of CD (MCD), the body often makes too much of a protein called interleukin-6 (IL-6). IL-6 normally helps regulate immune function. Too much IL-6 can cause lymphocytes to grow and divide too quickly. But it’s not clear what causes the high levels of IL-6.

One cause seems to be infection with human herpesvirus-8 (HHV-8), also known as Kaposi sarcoma herpesvirus (KSHV) (because it can cause Kaposi sarcoma). HHV-8 is often found in the lymph node cells in people who have MCD, especially those who are HIV positive. HHV-8 can cause infected cells to make a form of IL-6, which could explain how it leads to CD.

Many people are infected with HHV-8, but in people with normal immune systems the virus doesn’t seem to cause problems. People infected with HIV, however, often have weakened immune systems, which might allow HHV-8 to grow and cause problems. This could explain why people infected with HIV are more likely get MCD. Still, some people with HIV who develop MCD do not have weakened immune systems, so it’s not clear if this is the only reason.

HHV-8 hasn’t been found in all cases of MCD. And it’s not clear what causes the localized (unicentric) form of CD. Researchers are still looking for the causes of CD in these other cases.

The American Cancer Society medical and editorial content team

Our team is made up of doctors and oncology certified nurses with deep knowledge of cancer care as well as journalists, editors, and translators with extensive experience in medical writing.

National Organization for Rare Disorders. Castleman disease. Accessed at https://rarediseases.org/rare-diseases/castlemans-disease/  on January 5, 2018. 

Simpson D. Epidemiology of Castleman disease. Hematol Oncol Clin North Am. 2018;32(1):1-10.

Wu D, Lim MS, Jaffe ES. Pathology of Castleman disease. Hematol Oncol Clin North Am. 2018;32(1):37-52. 

Last Revised: February 8, 2018

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