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, though. 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.
There are two basic types of Castleman disease:
- Unicentric Castleman disease. This localized form of the disease affects only a single gland (lymph node) in your lymphatic system.
- Multicentric Castleman disease. This type affects multiple lymph nodes and lymphatic tissues, and can severely weaken your immune system.
Multicentric Castleman disease can be further classified as:
- Multicentric Castleman disease without POEMS syndrome
- Multicentric Castleman disease with POEMS syndrome that involves areas of abnormal bone (osteosclerotic lesions)
- Multicentric Castleman disease with POEMS syndrome without osteosclerotic lesions
Many people with Unicentric Castleman disease don't notice any signs or symptoms. The diseased lymph node is usually located in the chest, neck or abdomen. When signs and symptoms are present, they may include:
- A feeling of fullness or pressure in the chest or abdomen that can cause difficulty breathing or eating
- An enlarged lump under the skin in the neck, groin or armpit
- Unintended weight loss
- Less commonly, fever, night sweats and weakness
Most people with Multicentric Castleman disease experience:
- Night sweats
- Fatigue and weakness
- Loss of appetite
- Unintended weight loss
- Enlarged lymph nodes, usually around the neck, collarbone, underarm and groin areas
- Enlarged liver or spleen
Other, less common symptoms include:
- Nerve damage in the hands and feet that leads to numbness (peripheral neuropathy)
- Skin rash
It's not clear what causes Castleman disease. However, infection by a virus called human herpesvirus 8 (HHV-8) is associated with multicentric Castleman disease.
The HHV-8 virus has also been linked to the development of Kaposi's sarcoma, a cancerous tumor of the blood vessel walls that can be a complication of HIV/AIDS. Studies have found that HHV-8 is present in HIV-positive people who have Castleman disease, and in 40 to 50 percent of HIV-negative people with Castleman disease.
The precise role of HHV-8 is unclear. But it appears to cause malfunctioning immune system cells to reproduce rapidly. The immune system cells produce a protein called interleukin-6 (IL-6) that contributes to the overgrowth of lymphatic cells.
Castleman disease can affect anyone. But the average age of people diagnosed with unicentric Castleman disease is 35. Most people with the multicentric form are in their 50s and 60s. The multicentric form is also slightly more common in men than in women.
The only known risk factor for Castleman disease appears to be having HIV/AIDS.
People with unicentric Castleman disease often notice no signs or symptoms. The diseased lymph node may be found during screening or treatment for another illness.
If unicentric or multicentric Castleman disease is suspected, your doctor is likely to start with a thorough physical examination of your lymph nodes, to determine their size and consistency.
Your doctor may then recommend:
- Blood and urine tests, to help rule out other infections or diseases. These tests can also reveal anemia and abnormalities in blood proteins that are sometimes characteristic of Castleman disease.
- Imaging tests, to detect enlarged lymph nodes, liver or spleen. CT scan or MRI of your neck, chest, abdomen and pelvis may be used. Positron emission tomography (PET) scans also may be used to diagnose Castleman disease and to assess whether a treatment is effective.
- Lymph node biopsy, to differentiate Castleman disease from other types of lymphatic tissue disorders, such as lymphoma. A tissue sample from an enlarged lymph node is removed and examined in the laboratory. Depending on the location of the lymph node, the biopsy may be done under local anesthesia or during more extensive surgery.
Treatment depends on the type of Castleman disease you have.
Unicentric Castleman disease can be cured by surgery removing the diseased lymph node. If the lymph node is in your chest or abdomen — which is often the case — major surgery may be required. If surgical removal isn't possible, medication may be used to shrink the lymph node. Radiation therapy also may be an effective way to destroy the affected tissue. You'll need follow-up exams, including imaging, to check for relapse.
In Multicentric Castleman disease, surgery usually isn't an option because of the number of lymph nodes involved. However, surgery to remove an enlarged spleen may be an option to help ease symptoms.
Treatment generally involves medications and other therapies to control cell overgrowth. Specific treatment depends on the extent of your disease and on whether you have HIV or HHV-8 infection or both.
The options include:
- Monoclonoal antibodies, to block the action of the IL-6 protein that contributes to cell overgrowth. Your doctor may recommend initial treatment with a monoclonal antibody, such as siltuximab (Sylvant), if you don't have organ damage or HIV or HHV-8 infection.
- Chemotherapy, to slow overgrowth of lymphatic cells. Your doctor may recommend adding chemotherapy if the disease doesn't respond to monoclonal antibodies or if you have organ failure.
- Corticosteroids, to control inflammation.
- Antiviral drugs, to block the activity of HHV-8 or HIV if you have one or both of those viruses.
- Thalidomide (Thalomid), to block the action of the IL-6 protein. Thalidomide is an immune-system modulator that has been shown to be effective at inducing remission in Castleman disease.