Castleman disease

Castleman disease is a group of rare conditions that cause enlarged lymph nodes and a wide range of symptoms. The most common type affects a single lymph node, usually in the chest or neck. But it can occur in other areas. This form of the disease is called unicentric Castleman disease (UCD).

Multicentric Castleman disease (MCD) involves multiple regions of enlarged lymph nodes. It can cause inflammatory symptoms and issues with organ function. There are three types of MCD:

• HHV-8/KSHV-associated MCD. This type is linked to human herpesvirus type 8 (HHV-8), also called Kaposi's sarcoma-associated herpesvirus (KSHV). It often occurs in people with human immunodeficiency virus (HIV) or other causes of immune deficiency.
• Idiopathic MCD. The cause of this type is unknown. It is also called HHV-8-negative MCD. The most serious form of this type of MCD is known as iMCD-TAFRO. The name TAFRO comes from the first letter of its main symptoms. Thrombocytopenia is a low platelet count. Anasarca is swelling and fluid in the body. Fever or a higher level of C-reactive protein is a marker of inflammation. Reticulin fibrosis/renal dysfunction is scarring of the bone marrow and decreased function of kidneys. Organomegaly is organ swelling.
• POEMS-associated MCD. This type is linked to another condition called POEMS syndrome. POEMS syndrome is a rare blood condition that damages nerves and affects other parts of the body. The name POEMS comes from the first letter of its main symptoms. Polyneuropathy is numbness, tingling and weakness in the legs or hands caused by nerve damage. Organomegaly is an enlarged spleen, liver or lymph nodes. Endocrinopathy is atypical hormone levels. Monoclonal protein is a protein made by atypical plasma cells in bone marrow make. Skin changes may include a change in color and thickness or increased hair growth.

Sometimes, people may have 2 to 3 enlarged lymph nodes and mild symptoms that do not meet the standards used to diagnose for MCD. These people may have another disease, or they may have the recently described subtype of Castleman disease called oligocentric. This also is known as regional Castleman disease. This subtype is rare.

Treatment and outlook vary depending on the type of Castleman disease you have. Unicentric Castleman disease, which involves only one enlarged lymph node, can usually be successfully treated with surgery.

The best treatment for oligocentric Castleman disease, which involves a few enlarged lymph nodes and has limited symptoms, is not known. But it is thought to be similar to the treatment for unicentric Castleman disease.

Not all people with MCD respond to the first treatment. But medicines are available that can help treat HHV-8-associated MCD and idiopathic MCD.

Many people with unicentric Castleman disease don't notice any signs or symptoms. The enlarged lymph node may be found during a physical exam or an imaging test for a different issue.

Some people with unicentric Castleman disease might have signs and symptoms that are more often seen in multicentric Castleman disease. These may include:

When to see a doctor

If you notice an enlarged lymph node on the side of your neck or in your underarm, collarbone or groin area, talk with your healthcare professional. Also call your care team if you have a lasting sense of fullness in your chest or abdomen, fever, fatigue, or weight loss that you can't explain.

It's not clear what causes unicentric Castleman disease or idiopathic multicentric Castleman disease (MCD). But HHV-8-positive MCD is known to occur in people whose immune systems are weakened, including people with HIV.

Castleman disease can affect people of any age. People usually are diagnosed with Castleman disease during midlife, but it can happen at any age, including during childhood.

There are no known risk factors for unicentric Castleman disease or idiopathic multicentric Castleman disease. Infection with HIV or having a condition that decreases how well the immune system works raises the risk of having HHV-8-positive multicentric Castleman disease.

People with unicentric Castleman disease (UCD) usually do well once the affected lymph node is removed, and life expectancy is usually not changed. But people with this condition are at increased risk of developing a rare autoimmune condition called paraneoplastic pemphigus. This condition can be life-threatening. Paraneoplastic pemphigus causes blisters in the mouth and on the skin that are often misdiagnosed. Though the risk of developing paraneoplastic pemphigus is low, being checked for this condition is important if you have UCD.

Idiopathic multicentric Castleman disease can rapidly get worse and involve life-threatening issues with organ function. This requires critical care with a machine that helps with breathing, called a ventilator, and treatments that help with organ function, such as dialysis and transfusions.

HHV-8-positive multicentric Castleman disease may involve life-threatening infections and organ failure. People who also have HIV/AIDS can have worse outcomes.

After reviewing your medical history and doing a detailed physical exam, your healthcare professional may recommend:

• Blood and urine tests. These help rule out other infections or diseases. These tests also can find anemia and changes in blood proteins that can be typical of Castleman disease.
• Imaging tests. These tests can find enlarged lymph nodes or an enlarged liver or spleen. A CT scan of the neck, chest, abdomen and pelvis may be used. A positron emission tomography (PET) scan may help evaluate Castleman disease and monitor treatment response.
• Lymph node biopsy. This test is essential to diagnose Castleman disease and rule out related diseases, such as lymphoma. In a biopsy, a tissue sample from an enlarged lymph node is removed and looked at in a laboratory.

Treatment depends on the type of Castleman disease you have.

Unicentric Castleman disease

Surgery to remove the affected lymph node is the usual treatment for unicentric Castleman disease (UCD). If the lymph node is in the chest or abdomen, major surgery may be needed.

Surgery to remove the enlarged lymph node usually cures UCD. But the condition sometimes comes back. If surgery is not possible, you may need medicines typically used for multicentric Castleman disease. If medicines don't work, radiation therapy may be an option.

You'll likely need follow-up exams, including imaging and laboratory tests, to check that the disease hasn't come back.

Treatment of oligocentric Castleman disease, a rare subtype, is usually similar to that of UCD. But more research is needed.

HHV-8-positive multicentric Castleman disease

Rituximab (Rituxan, Ribani, others) is usually the first treatment for HHV-8-positive MCD. Rituximab is highly effective, but sometimes medicines called antivirals and chemotherapies are needed. Antiviral medicines can block the activity of HHV-8 or HIV, and chemotherapies can get rid of extra immune cells.

Idiopathic multicentric Castleman disease

Siltuximab (Sylvant) is usually the first treatment for idiopathic MCD. In the U.S., siltuximab is the only medicine approved by the Food and Drug Administration (FDA) for the treatment of idiopathic MCD. People who get better after taking siltuximab tend to have successful long-term treatment. This drug blocks the action of a protein called interleukin-6. The bodies of people who have idiopathic MCD produce too much of this protein.

People who are critically ill with idiopathic MCD often receive treatment with medicines called corticosteroids. They also may need chemotherapy. Corticosteroids such as prednisone can help control inflammation. Chemotherapy can get rid of immune cells that are causing issues.

When siltuximab doesn't work, other treatments such as rituximab (Rituxan, Ribani, others) and sirolimus (Rapamune) may be used.

You may be referred to a doctor trained in treating blood conditions. This type of doctor is called a hematologist.

What you can do

• Write down the symptoms you have had and how long you've had them.
• Write down key medical information, including other health conditions.
• Make a list of all medicines, vitamins and supplements that you're taking, including the doses.

Questions to ask your doctor

• What's the most likely cause of my symptoms?
• What kinds of tests do I need? Do they need any special preparation?
• What treatment do you recommend? Do I need surgery?

In addition to the questions that you've prepared to ask your healthcare professional, don't hesitate to ask other questions during your appointment.

What to expect from your doctor

Your healthcare team is likely to ask you a number of questions. Being ready to answer these questions may leave time to go over points you want to spend more time on. You may be asked:

• When did you first have symptoms?
• Have your symptoms been ongoing or do they come and go?
• How bad are your symptoms?
• Does anything seem to improve your symptoms?
• What, if anything, seems to worsen your symptoms?
• Do you have any other health conditions, such as lymphoma, HIV/AIDS or Kaposi sarcoma?