What is Castleman disease?

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Unicentric Castleman disease is the more common type of this condition and affects the lymph nodes.

Lymph nodes — typically found throughout the body — are part of the body’s immune system. These clusters contain immune cells that can fight infection or cancer.

The unicentric disease can develop either as a single enlarged lymph node or multiple enlarged lymph nodes in a single bodily region, such as the neck, abdomen, or chest.

Multicentric Castleman disease presents as enlarged lymph nodes throughout the body. Consequently, the symptoms are more severe.

There are also two subtypes — those that link to the human herpesvirus-8 (HHV-8), which are HHV-8-positive, and those that are HHV-8-negative. Another name for the latter type is idiopathic, which means the cause is unknown.

The HHV-8-positive subtype affects 25–50% of multicentric cases, while the HHV-8-negative subtype affects 50–75% of cases.

Learn more about HHV-8, or Kaposi sarcoma.

Below are symptoms of some types of Castleman disease.

Unicentric

Most people with unicentric Castleman disease do not have symptoms. If symptoms do appear, they are usually mild and result from compression of the enlarging lymph nodes on surrounding structures.

Occasionally, individuals may experience symptoms that are likely due to the location and size of the growth. For example, if the growth develops next to a vein, it could produce a bulge in the blood vessel and obstruct blood flow.

Less common signs and symptoms include those relating to systemic inflammation. These include:

• fever
• excessive sweating
• rash
• tiredness
• weight loss
• low hemoglobin, a protein in red blood cells that transports oxygen
• high C-reactive protein, a sign of acute inflammation

Multicentric

Symptoms and signs of idiopathic multicentric Castleman disease include:

• flu-like symptoms, such as:
  • fever
  • weight loss
  • night sweats
  • tiredness
  • nausea
  • vomiting
  • loss of appetite
• an enlarged liver or spleen
• fluid buildup in the abdomen or other signs of fluid buildup
• atypically large lymph nodes, particularly in the:
  • groin
  • armpit
  • neck
  • collarbone
• eruptive cherry hemangiomas, which are the sudden development of skin growths
• numbness in the feet and hands
• kidney dysfunction
• anemia, or low red blood cells
• high C-reactive protein and other inflammatory markers
• low or high platelets, the fragments of blood cells that enable typical clotting
• low albumin, a protein the liver makes
• high immunoglobulins or gamma globulins, substances containing antibodies that promote the immune response

People with the HHV-8-positive subtype have many large lymph nodes and episodes of inflammation that cause symptoms. Since this form commonly affects those with compromised immunity — such as people with HIV— they may also manifest other symptoms of their condition.

Researchers know very little about what causes Castleman disease. However, some evidence suggests that it may result from impaired immunoregulation or immunodeficiency.

Immunoregulation refers to the body’s system of maintaining a balance between immune activation and suppression. Conversely, immunodeficiency involves an absence or problem in parts of the functioning of the immune system.

Infection with the HHV-8 virus is a known cause of the HHV-8-positive multicentric type. Additionally, having HIV or another condition that compromises the immune system may increase the risk.

Risk factors

For both types of Castleman disease, there are no known risk factors. Certain foods, lifestyle practices, or environmental exposure are unlikely to have links to this condition.

Diagnosis is difficult because Castleman disease is rare and shares similarities with other conditions. However, the following tests may be beneficial to help determine if a person has the condition:

• Lymph node biopsy: This involves examining a sample tissue from a lymph node under a microscope to identify distinctive features that could suggest the condition.
• Imaging tests: PET-CT — a type of CT scan — and X-rays can help locate enlarged lymph nodes.
• Lab tests: Routine and specialized tests may help rule out other conditions. Some tests include:
  • a complete blood count
  • testing for HIV and HHV-8
  • markers of organ function, such as creatinine, an indicator of kidney function, and albumin, an indicator of liver or kidney function

Treatment may depend on whether the person has unicentric or multicentric Castleman disease:

Unicentric

The first-line treatment involves surgically removing the affected lymph nodes. Although this usually results in a cure, health experts have reported that the condition may recur in some cases.

However, it is not always possible to remove the lymph nodes due to their location. For these cases, doctors opt to treat the symptoms of the condition. Treatment would involve one or more of the following:

• If symptoms stem from an inflammatory syndrome, the treatment may entail anti-interleukin-6 therapy with siltuximab (Sylvant), which targets a protein that plays a role in inflammation.
• If symptoms are due to compression, the treatment may entail rituximab (Rixathon), which targets and eliminates a certain type of immune cell.
• If the above options do not produce effective results, radiation therapy may be necessary.

Idiopathic, or HHV-8-negative, multicentric

The treatment of choice for idiopathic multicentric is siltuximab (Sylvant), which is effective in 34–50% of people. For those who do not respond to this approach, doctors may advise:

• rituximab (Rixathon)
• chemotherapy regimens for blood cancers
• autoimmune disease treatments

HHV-8-positive multicentric

First-line treatment is rituximab (Rixathon). It is very effective, but sometimes cytotoxic chemotherapy, antiviral agents, or both are necessary.

The complications of Castleman disease may depend on the type.

The two most serious ones in the unicentric type are paraneoplastic pemphigus (PNP) and lung abnormalities, such as bronchiolitis obliterans (BO). PNP is an autoimmune disease that is often fatal, while BO is a condition that obstructs the small airways of the lungs.

The main complications relating to the multicentric form of the condition include:

• thromboembolic disorders, which obstruct a blood vessel due to a dislodged clot
• internal organ involvement of the kidneys or liver
• inflammatory reactions

Some of these complications can be life threatening in people with multicentric Castleman disease.

A 2017 study in China reports that surgically removing the affected lymph nodes in unicentric Castleman disease leads to a cure in most cases. However, researchers have not established an optimal treatment for the multicentric form, so the outcome is less favorable.

Generally, a person’s life expectancy does not change by having unicentric Castleman disease. However, this may not be the case for the multicentric type. Older research indicates that the 5-year overall survival rate for HHV-8-positive multicentric disease in people who are also HIV-negative is 65%.

Additionally, people who are HIV-positive tend to have worse outcomes.

However, newer treatments can help improve the 5-year survival of individuals with multicentric disease.

Castleman disease is a condition that involves the enlargement of lymph nodes. The more common type — unicentric— only affects one lymph node or one area of the body. However, the less common type — multicentric — affects many lymph nodes throughout the body.

Some evidence suggests that Castleman disease may stem from dysfunction in the body’s regulation of the immune system or a deficiency in this system. People with an HHV-8 infection are more likely to develop the condition.

Treatment is very effective for the unicentric type but much less so for the multicentric form of the condition. Consequently, unicentric is often curable, and the outlook for multicentric is less favorable.