Castleman Disease

What is Castleman disease?

Castleman disease refers to a group of rare disorders that involve a hyperactive immune system. In people who are healthy, their immune system activates to fight off invaders like bacteria or viruses but then settles back down, watching and waiting for the next time it’s needed. In people with Castleman disease, their immune system continues to remain activated and leads to a chronic hyper-inflammatory state that can damage multiple organs and even cause death.

Lymph nodes (tiny organs) work with your immune system to filter substances from your body. When you’re sick, your lymph nodes work harder to clear the bacteria or virus, along with the cells your body makes to fight them. This causes an overgrowth of cells in your lymph nodes, making these nodes bigger (swell).

In Castleman disease, one or more of your lymph nodes become enlarged. And they don’t just get bigger. When your doctor looks at a sample of your lymph node (a biopsy) under a microscope or analyzes them using different staining, they can see changes in the tissue.

What are the different types of Castleman disease?

Castleman disease is currently classified as unicentric or multicentric based on how many regions of your body have enlarged lymph nodes. The differences between unicentric and multicentric Castleman disease are important because each type requires different treatments.

Unicentric Castleman disease (UCD)

Unicentric Castleman disease (UCD) — or localized Castleman disease — causes enlargement of one or more lymph nodes in one area (region) of your body. The causes of UCD are unknown.

Multicentric Castleman disease (MCD)

Multicentric Castleman disease (MCD) causes lymph node enlargement in multiple regions of your body. There are three categories of MCD: POEMS-associated MCD, HHV-8-associated MCD and idiopathic MCD.

• POEMS-associated MCD: POEMS is a rare blood disorder that sometimes accompanies MCD. POEMS gets its name from its associated signs and symptoms. They include polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder and skin changes.
• HHV-8-associated MCD: Human herpes virus-8 (HHV-8) is a common virus. Most people who have it don’t get sick. You’re more likely to have HHV-8-associated MCD if you’re HIV positive or if you have another condition that makes you more susceptible to infections (immunocompromised).
• Idiopathic MCD (iMCD): The most common form of MCD is idiopathic. “Idiopathic” means that its causes are unknown.

There are three types of iMCD:

• iMCD associated with TAFRO: TAFRO syndrome sometimes accompanies iMCD. TAFRO gets its name from its associated signs and symptoms, including thrombocytopenia (low platelets), anasarca (swelling from fluid build-up), fever, renal (kidney) dysfunction and organomegaly (enlarged spleen or liver).
• iMCD with idiopathic plasmacytic lymphadenopathy (iMCD-IPL): People with IMCD-IPL may have too many platelets in their blood (thrombocytosis), and their white blood cells may make too many proteins called antibodies.
• iMCD, not otherwise specified (iMCD-NOS): iMCD-NOS has unknown causes and isn’t associated with TAFRO or POEMS.

Is Castleman disease a cancer?

Research on Castleman disease is ongoing. Certain autoimmune conditions, cancers or infections can present with changes in lymph nodes or clinical features that closely resemble Castleman disease. It’s unknown whether Castleman disease should be considered an autoimmune disease, cancer or infectious disease.

Who does Castleman disease affect?

Castleman disease can affect anyone. UCD is more commonly diagnosed in people in their 30s and 40s. MCD is more common in people in their 50s and 60s. While UCD affects people equally regardless of sex, MCD is slightly more common in men and people assigned male at birth (AMAB).

How common is Castleman disease?

Castleman disease is rare, with approximately 4,300 to 5,200 new cases diagnosed in the United States each year. About 75% of these cases are UCD, and the remaining 25% are MCD.

What causes Castleman disease?

While the causes of UCD are unknown, an HHV-8 infection is associated with MCD. You’re at greater risk of developing HHV-8-associated MCD if you have HIV or another condition that may make it difficult for your immune system to fight the HHV-8 virus.

Scientists are researching potential causes of UCD and iMCD, including infections other than HHV-8, gene mutations and autoimmune responses.

What are the symptoms of Castleman disease?

Signs and symptoms of Castleman disease vary depending on the type. For example, you likely won’t have symptoms with unicentric Castleman disease, and enlarged lymph nodes may be the only sign. Your healthcare provider may not suspect UCD until they notice lymph node enlargement during imaging for another issue. When symptoms occur, they may result from an enlarged lymph node creating pressure on a nearby organ.

MCD is much more likely to cause noticeable changes.

Signs and symptoms of MCD include:

• Fever.
• Night sweats.
• Nausea and vomiting.
• Unexplained weight loss.
• Fatigue (extreme tiredness).
• Abnormally large lymph nodes.
• Enlarged spleen (splenomegaly).
• Enlarged liver (hepatomegaly).
• Numbness in your hands and feet.
• Swelling in your feet and ankles.
• Swelling in your abdomen.
• Anemia (low amount of red blood cells).

How is Castleman disease diagnosed?

Castleman disease symptoms are similar to other conditions, including common illnesses like the flu. Your healthcare provider may perform various tests to rule out these conditions. They’ll perform additional tests to determine the type of Castleman disease.

Tests and procedures may include:

• Biopsy: A lymph node biopsyis the only way to confirm you have the typical pathological changes associated with Castleman disease. During a biopsy, your provider removes a tissue sample from a lymph node — or the entire lymph node — and examines it under a microscope to identify pathological features of Castleman disease. They’ll perform a test on the tissue to check for the presence of HHV-8. The results will determine whether you have HHV-8-associated MCD or another type of Castleman disease.
• Blood and urine tests: Your provider may take a blood or urine sample to check for signs of MCD. For example, they may check your blood cells to look for signs of anemia (low red blood cell count), thrombocytosis (high platelet count) or thrombocytopenia (low platelet count). Abnormal blood cell counts are associated with some forms of Castleman disease. Your provider may perform an HIV test. An HIV-positive result is typical with HHV-8-associated MCD.
• Imaging tests: Tests such as X-rays, CT scans, MRIs and PET scans allow your healthcare provider to locate enlarged lymph nodes in your body. Imaging can also show other signs of Castleman disease, like an enlarged spleen or liver.

How is Castleman disease managed or treated?

Treatment for Castleman disease varies according to the type.

Unicentric Castleman disease (UCD) treatment

Surgery to remove the affected lymph nodes is the primary treatment for UCD. Depending on where the lymph nodes are located or if they’re too big, you may need to receive radiation therapy or immunotherapy before surgery for UCD. These therapies shrink the growths on your lymph nodes, making them easier to remove.

If surgeons can’t remove the tumor and you don’t have symptoms, your provider may prefer to monitor your tumor instead of treating it immediately. If surgery isn’t an option and you have symptoms, your provider may recommend treatments for multicentric Castleman disease.

Multicentric Castleman disease (MCD) treatment

MCD is more difficult to treat than UCD. Because the multicentric type is widespread, healthcare providers don’t typically use surgery or radiation to treat it. Instead, treatment depends on whether you have HHV-8 and how severe the disease is.

Your provider may use:

• Corticosteroids: Medications that reduce inflammation and help provide symptom relief. This is usually recommended in people who are critically ill to quickly manage the inflammation.
• Chemotherapy drugs: Anticancer medications that slow the overgrowth of cells in your lymphatic system. Rituximab is a commonly prescribed medication used to treat HHV-8-associated MCD.
• Immunotherapy: Humanized monoclonal antibodies (proteins that help fight infections) that boost the immune system. In 2014, siltuximab (Sylvant ®) became the only iMCD therapy approved for use by the U.S. Food and Drug Administration (FDA). This treatment works by blocking a protein that fuels cell growth in MCD.
• Antiviral drugs: Medicines used to treat HIV or HHV-8. You may need antiviral drugs and other treatments if you have HHV-8-associated MCD and another infection.

What complications are associated with Castleman disease?

Castleman disease increases your chances of developing cancer, including lymphoma (cancer of the lymph system).

MCD can increase your risk of developing infections that can damage organs and even be life-threatening without treatment.

Your healthcare provider will closely monitor your condition, tailoring your treatment to prevent complications whenever possible.

What are the risk factors for Castleman disease?

There aren’t any known risk factors for UCD or iMCD. People with the human immunodeficiency virus (HIV) or a weakened immune system are at higher risk of developing HHV-8-associated MCD.

Can Castleman disease be prevented?

There aren’t any known risk factors for most types of Castleman disease, so there’s nothing you can do to prevent them.

What is the life expectancy of someone with Castleman disease?

The outlook is very good for most people with UCD. Removing the affected lymph node is often enough to cure it. With treatment, UCD doesn’t usually affect life expectancy.

The prognosis for people with MCD depends on the type of MCD and how serious the disease is. Some people have intense flares that can be life-threatening. Others have more chronic symptoms. About 65% to 75% of people diagnosed with MCD are still alive five years later — and with breakthrough therapies, there’s hope that the outlook will continue to improve.

Talk to your provider about how your form of Castleman disease and other factors like another disease or condition may impact your outlook.

When should I call the doctor?

Contact your healthcare provider if you find a lump in your neck, armpit or groin or experience other symptoms of Castleman disease that don’t go away after a few weeks. Symptoms of Castleman disease often overlap with symptoms of other, more common illnesses. Your doctor will only diagnose it after a lymph node biopsy shows features of Castleman disease and evaluates and excludes other illnesses that might be causing your symptoms.

What questions should I ask my doctor?

Questions you should ask your healthcare provider include:

• Which type of Castleman disease do I have?
• What kinds of tests should I get?
• What’s the best treatment for me?
• What treatment side effects should I expect?
• What symptoms will alert me of a complication associated with Castleman disease?

A note from Cleveland Clinic

Castleman disease causes abnormal growths in your lymph system. Your symptoms and treatment options depend on the type of Castleman disease you have. Additional conditions like HIV or associated disorders — like TAFRO and POEMS — will also shape your experience. In some instances, surgery and careful monitoring may be the only treatment you need. Or you may need a combination of treatments throughout your lifetime to prevent the risk of significant complications. Ask your healthcare provider how your condition will impact your treatment and outlook.