Castleman disease

Definition

Castleman disease is a rare illness that affects your lymph nodes and other immune-cell structures of your body.

It's classified as a lymphoproliferative disorder, which means it involves a proliferation, or overgrowth, of lymphatic cells. This makes it similar in many ways to cancers of the lymphatic system (lymphomas), which are also characterized by cell overgrowth. Castleman disease isn't considered a cancer, however.

The disease is named after the American pathologist who first described it in the 1950s. Other names for Castleman disease are giant lymph node hyperplasia and angiofollicular lymph node hyperplasia.

Castleman disease can occur in a localized or a more widespread form. Treatment and outlook depend on which type of Castleman disease you have.

Symptoms

There are basically two types of Castleman disease:

• Unicentric Castleman disease. This localized form of the disease affects only a single lymph node.
• Multicentric Castleman disease. This type affects multiple lymph nodes and lymphatic tissues, and can severely weaken your immune system. It sometimes accompanies HIV infection and AIDS.

The two different types of Castleman disease affect people very differently.

Unicentric Castleman disease
Many people with unicentric Castleman disease notice no symptoms at all. Most often, the diseased lymph node is located in the chest or abdomen. When there are signs and symptoms, they may include:

• A feeling of fullness or pressure in the chest or abdomen that can cause difficulty breathing or eating
• Low-grade fever
• Weight loss
• Night sweats
• Anemia, which may be revealed through a blood test

Multicentric Castleman disease
People with multicentric Castleman disease usually develop systemic signs and symptoms including:

• Fever
• Night sweats
• Weight loss
• A general feeling of discomfort (malaise)
• Weakness or fatigue from anemia
• Enlarged peripheral lymph nodes, usually around the neck, collarbone, underarm and groin areas
• Enlarged liver or spleen
• Nerve damage in the hands and feet that leads to numbness or weakness (peripheral neuropathy)

Causes

Doctors are still trying to determine the exact cause of Castleman disease, but many suspect infection by a virus called the human herpes virus 8 (HHV8). This virus has been associated with Kaposi sarcoma, a cancerous tumor of the blood vessel walls. It's not uncommon for a person with multicentric Castleman disease to also have Kaposi sarcoma, especially if the person is also HIV-positive.

So far, studies have shown that HHV8 is found in most people with multicentric Castleman disease who are HIV-positive and in about half of people with the disease who are HIV-negative. But only one case of unicentric Castleman disease has been associated with HHV8.

Another potential contributor to the disease may be a type of protein produced by immune cells called interleukin-6 (IL-6). It's possible that HHV8, or some other unidentified factor, may stimulate overproduction of IL-6, leading to an overgrowth of lymphatic cells.

Risk factors

There seem to be no clear-cut risk factors for Castleman disease. The disease can affect anyone — adults and children, men and women. The average age of people with unicentric Castleman disease is around 30 or 40, whereas most people with the multicentric form are in their 50s and 60s.

When to seek medical advice

If you notice an enlarged lymph node on the side of your neck, in your underarm, collarbone or groin area, talk to your doctor. Also, call your doctor if you have other signs or symptoms, such as a feeling of fullness in your chest or abdomen, fever, fatigue or unexplained weight loss. These signs and symptoms are common to many different types of illnesses. See your doctor to determine the underlying cause.

Tests and diagnosis

A number of tests can help your doctor determine if you have Castleman disease, although unicentric Castleman disease is often found incidentally. People with unicentric Castleman disease often notice no symptoms, and the diseased lymph node is found during screening or treatment for other illnesses, such as during a CT scan or during abdominal or chest surgery.

Tests your doctor may conduct to obtain a diagnosis of either unicentric or multicentric Castleman disease include:

• Physical examination. Your doctor may examine not only your swollen lymph nodes but also your other lymph nodes to determine their size and consistency.
• Blood and urine tests. Blood and urine tests may help your doctor rule out other infections or diseases. They can also reveal anemia and abnormalities in blood proteins that are sometimes characteristic of Castleman disease.
• Imaging techniques. An X-ray, computerized tomography (CT) scan or magnetic resonance imaging (MRI) scan of your chest, neck, abdomen and pelvis may detect the presence and number of enlarged lymph nodes. These tests can also determine whether organs such as your liver or spleen are enlarged.
• Lymph node biopsy. To differentiate Castleman disease from other types of lymphatic tissue disorders, such as lymphoma, it's necessary to take a sample of lymph node tissue for examination in the laboratory. If the enlarged lymph node is close to the surface of your skin, the biopsy can be done under local anesthesia. If it's in your chest or abdomen, more extensive surgery may be necessary to access the lymph node. By looking at the structure of the cells, a doctor who specializes in diagnosing disease (pathologist) may be able to tell whether it's lymphoma or Castleman disease.

Castleman disease is rare, so you may need a second opinion. Special cell-identifying techniques may help with the diagnosis.

Complications

People with unicentric Castleman disease usually do well once the affected lymph node is removed, although having Castleman disease may increase your risk of lymphoma.

Multicentric disease, on the other hand, is much more serious. People with multicentric disease have an average survival of about two years after the disease begins. Death usually occurs due to a serious infection, failure of multiple organs or cancer, such as lymphoma or Kaposi sarcoma. The presence of HIV tends to worsen the outcome.

Treatments and drugs

Treatment depends largely on the type of Castleman disease you have. Treatment for unicentric Castleman disease is almost always with surgery, while multicentric Castleman disease requires more systemic therapies.

Unicentric Castleman disease
Unicentric Castleman disease can be cured by surgically removing the diseased lymph node. If the lymph node is in your chest or abdomen — which is often the case with unicentric disease — major surgery may be required to remove the node. This usually involves a hospital stay. If the affected node is in a place that's easy to access, such as in your underarm area or your neck, a simpler procedure may be performed that doesn't require hospitalization. But this is less common.

If surgical removal isn't possible, such as if the lymph node is difficult to get to, radiation therapy may be an effective way to destroy the affected tissue.

Multicentric Castleman disease
Treating multicentric Castleman disease is generally more difficult. Because the disease is rare, has varied nonspecific signs and symptoms, and spontaneously goes into remission at times, doctors have found it difficult to identify the best treatment. In addition, there are no clinical trials that offer definitive evidence in favor of any therapy.

Most therapies are palliative, which means their goal is to relieve signs and symptoms rather than cure the illness. Surgery usually isn't an option for multicentric disease because of the number of lymph nodes involved, although sometimes removing an enlarged spleen may help ease symptoms.

Therapies that are commonly used for multicentric disease, with varying degrees of success, include the following regimens. Doctors generally try as many therapies as they can to provide the most relief.

• Corticosteroids. The basic function of corticosteroid therapy is to control inflammation. With multicentric Castleman disease, doctors usually prescribe steroids, such as prednisone, in combination with other therapies. Long-term use of steroids tends to reduce your resistance to infections, though, and carries certain risks, including a high risk of bacterial infection.
• Chemotherapy. Anti-cancer drugs (chemotherapy), taken by injection into a vein or by mouth, may provide relief from symptoms. Anti-cancer drugs can be useful because they target rapidly reproducing cells, such as those associated with Castleman disease. If chemotherapy is stopped, though, symptoms tend to come back and further treatment is needed to maintain symptom relief. Still, chemotherapy has helped the disease go into remission for a few people. Usually, doctors use a combination of anti-cancer drugs.
• Antiviral drugs. Antiviral medications, such as ganciclovir (Cytovene), are known to inhibit the activity of the virus HHV8. The success of this therapy has been mixed, being effective for some people but not for others. Doctors still have many questions about antiviral therapy for Castleman disease, such as which antiviral is best and when the best time to administer it is.
• Monoclonal antibodies. These man-made antibodies are designed to zero in on specific cells in the body that aren't working right. One such antibody that may be effective for multicentric Castleman disease works by neutralizing or blocking the activity of IL-6, the immune-cell protein suspected of playing a role in causing the disease. Another monoclonal antibody that may help is rituximab (Rituxan), a drug that targets a different type of cell associated with Castleman disease.
• Immune modulators. Doctors have tried other drugs that help to regulate your immune system (immune modulators) in the hopes that these drugs might have some effect. Interferon alpha has both immunoregulatory and antiviral effects and has been used successfully in a few people with Castleman disease, although symptoms usually return once you stop taking the drug. Thalidomide, a powerful immunomodulatory drug, also has helped a few people and may help decrease the production of IL-6.

Coping and support

Because Castleman disease occurs only rarely, it can be difficult to discover you have the illness. Dealing with multicentric disease, in particular, can be challenging. Some people with Castleman disease may have to deal with multiple diseases, including HIV infection, AIDS and Kaposi sarcoma. In the face of a serious illness, it often helps to:

• Learn all you can about your condition. Find out how the disease progresses, your prognosis and your treatment options, including both experimental and standard treatments and their side effects. The more you know, the more active you can be in your own care.
• Be proactive. Although you may often feel tired and discouraged, don't let others — including your family or your doctor — make important decisions for you. Take an active role in your treatment.
• Maintain a strong support system. Strong relationships are crucial in dealing with life-threatening illnesses. In addition to friends and family, a counselor, spiritual advisor, or a support group also can be helpful.