HHV8-associated multicentric Castleman’s disease

by Jason Wasserman MD PhD FRCPC and David Li MD
June 1, 2025

HHV8-associated multicentric Castleman’s disease (also called KSHV/HHV8-associated multicentric Castleman disease) is a condition in which the immune system creates a large number of abnormal cells called plasmablasts, due to infection by a virus known as human herpesvirus-8 (HHV8). This leads to enlarged lymph nodes, inflammation throughout the body, and systemic symptoms, such as fever and fatigue. Unlike other forms of Castleman’s disease, which only affect one lymph node, this form affects multiple lymph nodes and sometimes other organs, such as the spleen or bone marrow. It commonly occurs in patients who have weakened immune systems, such as those living with HIV.

What are the symptoms of HHV8-associated multicentric Castleman’s disease?

People with HHV8-associated multicentric Castleman’s disease typically experience:

  • Persistent fever.

  • Fatigue and weakness.

  • Unintentional weight loss.

  • Muscle aches (myalgias).

  • Enlarged lymph nodes throughout the body.

  • Enlarged spleen and liver.

  • Fluid build-up in the body (edema or effusions).

Some patients also develop a type of cancer called Kaposi sarcoma, caused by the same virus. Some individuals may also develop lymphoma, a type of cancer involving the lymph nodes or other tissues.

What causes HHV8-associated multicentric Castleman’s disease?

This disease is caused primarily by infection with a virus called human herpesvirus-8 (HHV8), also known as Kaposi sarcoma-associated herpesvirus (KSHV). HHV8 infects a specific type of immune cell, known as a plasmablast, causing these cells to multiply uncontrollably. These infected cells produce chemicals (cytokines) that cause widespread inflammation, leading to many of the disease’s symptoms. People whose immune systems are already weakened, especially those with HIV, have a higher risk of developing this disease. Genetic factors and aging-related immune weakening can also contribute to its development.

What is the difference between multicentric and unicentric Castleman’s disease?

Unicentric Castleman’s disease affects only a single lymph node or one region of lymph nodes and usually does not cause widespread symptoms. This form can often be cured by surgically removing the affected lymph node.

Multicentric Castleman’s disease, including the HHV8-associated form, affects multiple lymph nodes and can involve multiple organs. It causes widespread symptoms and systemic inflammation throughout the body, and generally requires systemic treatment (such as medications that target the immune system or the HHV8 virus itself).

Is HHV8-associated multicentric Castleman’s disease a type of cancer?

HHV8-associated multicentric Castleman’s disease itself is not considered cancer, but it is a serious condition that behaves similarly to certain cancers. It is known as a “lymphoproliferative disorder,” meaning that certain types of immune cells multiply excessively. Importantly, patients with this condition have an increased risk of developing cancers, such as lymphoma (a cancer of the lymph nodes or immune cells) and Kaposi sarcoma (a cancer caused by HHV8 infection).

How is this diagnosis made?

HHV8-associated multicentric Castleman’s disease is diagnosed by examining a lymph node biopsy under a microscope. Pathologists look for specific changes, including an increased number of abnormal immune cells called plasmablasts, which contain the HHV8 virus. These plasmablasts typically cluster in specific areas within the lymph node. Pathologists also examine the overall appearance of the lymph node to determine if it matches the patterns commonly associated with Castleman’s disease.

What additional tests may be performed to confirm the diagnosis?

Immunohistochemistry (IHC)

Immunohistochemistry is a special laboratory test that pathologists use to detect specific proteins within cells. For HHV8-associated multicentric Castleman’s disease, IHC is used to identify HHV8 by detecting a viral protein called latency-associated nuclear antigen (LANA) within plasmablast cells. This test confirms that these abnormal cells are infected by the HHV8 virus.

Additional blood tests

Your doctor may also perform blood tests to measure levels of inflammatory chemicals (cytokines), such as interleukin-6 (IL-6), and the HHV8 viral load, which help confirm the diagnosis and monitor the disease over time.

What is the prognosis for someone diagnosed with HHV8-associated multicentric Castleman’s disease?

HHV8-associated multicentric Castleman’s disease is usually a chronic, lifelong condition that tends to have periods of flare-ups (times of active inflammation and symptoms) followed by remission (times when symptoms improve or disappear). In the past, patients often had poor outcomes, with survival typically under two years after diagnosis.

Today, prognosis is much better, especially for people receiving modern treatments. Effective treatments include medications such as rituximab, which targets and reduces the abnormal immune cells. For HIV-positive patients, controlling HIV with antiretroviral therapy (ART) significantly improves prognosis. Early diagnosis and careful ongoing management significantly reduce the risk of complications, including the development of lymphoma or Kaposi sarcoma.

Questions to ask your doctor

  • Which tests confirmed my diagnosis of HHV8-associated multicentric Castleman’s disease?

  • Is my immune system weakened in any way?

  • Do I need additional testing to look for other related conditions, like Kaposi sarcoma or lymphoma?

  • What treatment options are available for me, and what side effects should I expect?

  • How often will I need follow-up visits or tests?

  • What symptoms should I monitor closely at home?

  • How can I best manage flare-ups or episodes of symptoms?

  • What is my risk of developing lymphoma or other complications?

  • Are there lifestyle changes or precautions I can take to help manage this condition?

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