Castleman Disease Treatment, Diagnosis, Prognosis & Symptoms

Facts you should know about Castleman disease

• Castleman disease is a rare condition affecting lymph nodes, and actually is a group of related conditions.
• Castleman disease is not cancer, although some of the methods used to treat Castleman disease also are used to treat cancers.
• There are two main forms of Castleman disease, unicentric (localized) and multicentric (found in different sites throughout the body).
• Signs and symptoms of Castleman disease occur most often with the multicentric form and can include
• The diagnosis of Castleman disease involves examination of a tissue sample (biopsy) by a pathologist.
• Treatment for Castleman disease is complex, and can involve a number of different types and classes of medications such as chemotherapy drugs, immunotherapy drugs, immunomodulator drugs, anti-viral drugs, and corticosteroids.
• Surgery may be used to treat unicentric Castleman disease or to help relieve symptoms in the multicentric form.
• Radiation therapy is another form of treatment sometimes used to destroy the abnormal tissue in Castleman disease.
• Giant lymph node hyperplasia and angiofollicular lymph node hyperplasia (AFH) are other names for Castleman disease.

What is Castleman disease?

Castleman disease is a rare disease of lymph nodes and similar tissues.
Sometimes referred to as Castleman’s disease, it is actually a group of
so-called lymphoproliferative disorders, meaning disorders that are accompanied
by abnormal growth (or proliferation) of the lymphatic tissue. The lymphatic (or
lymphoid) tissue consists of different types of cells that are involved in the
immune response, predominantly white blood cells known as lymphoctyes. Lymphatic
tissue is found in lymph nodes, the tonsils, thymus, spleen, bone marrow, and
gastrointestinal (GI) tract.

Abnormal growth of lymphoid tissue also is characteristic of lymphoma, a type
of cancer, but Castleman disease is not cancer. Other names for Castleman
disease are giant lymph node hyperplasia and angiofollicular lymph node
hyperplasia (AFH).

Even though Castleman disease is not considered to be cancer, one type of
this disease (multicentric Castleman disease, see below) behaves very much like
lymph node cancer (lymphoma), and can lead to serious health risks.

What are the signs and symptoms of Castleman disease?

There are no predictable signs and symptoms that suggest a person has Castleman disease.
Some people with the condition do not show any signs or symptoms, while others
will have a variety of symptoms.

Castleman disease has two forms, unicentric and multicentric.

Unicentric Castleman disease symptoms and signs

• Unicentric Castleman disease is localized and generally does not cause
  symptoms, although some affected people may have the symptoms associated with
  the multicentric form.
• People with unicentric Castleman disease have enlargement
  of lymph nodes in one area of the body.
• This form is much more common than multicentric Castleman disease, and is more likely to affect younger people.

Multicentric Castleman symptoms and signs

• Multicentric Castleman disease is more widespread, with abnormal enlargement
  of lymph nodes in locations throughout the body.
• In addition to noticeable
  swollen lymph nodes, other symptoms may be present, including:

What causes Castleman disease?

Castleman disease occurs when there is abnormal growth of the type of white
blood cell known as lymphocytes. However, the exact reasons for this abnormal
growth are not well understood. Elevated levels of a chemical associated with
the normal immune response, known as interleukin-6 (IL-6), often is found in
people with multicentric Castleman disease. People with multicentric Castleman
disease often are found to have a virus known as human herpesvirus-8 (HHV-8),
also known as Kaposi sarcoma herpesvirus (KSHV). HHV-8 is often found in the
lymph node cells in people with multicentric Castleman disease, especially in
those who are
HIV positive. This may be the reason for the elevated levels of
IL-6.

HHV-8 has not been seen in all cases of multicentric Castleman disease, and
many people become infected with HHV-8 and do not develop Castleman disease, so
the exact relationship between the viral infection and the condition is not
fully understood.

Is Castleman disease inherited (genetic)?

No, Castleman disease is not considered to be an inherited condition.

What are the types of Castleman disease?

The two types of Castleman disease are 1) unicentric, and 2) multicentric Castleman
disease, as described previously.

What are the stages of Castleman disease?

Since Castleman disease is not a cancer, there is not a formal staging system
(the stage of a cancer refers to the extent to which it has spread in the body).
The two types – multicentric and unicentric (see above) – refer to the extent of
disease in the body.

What is the prevalence of Castleman disease?

Castleman disease is rare, and there are no reliable estimates of its
frequency in the population.

Is there a test to diagnose Castleman disease?

The diagnosis of Castleman disease is made by a tissue sampling (biopsy) of
an affected lymph node. The tissue sample is examined by a pathologist (a
physician specialized in the diagnosis of diseases from tissue samples) under a
microscope, and additional special tests may be done on the tissue sample. A
number of blood tests that evaluate immune function may also be performed, but
the diagnosis itself depends upon identifying the abnormal lymph node tissue.

What is the treatment for Castleman disease?

Treatment for Castleman disease can involve a combination of different
approaches, including:

• Surgery to remove involved lymph nodes
  (see surgery section)
• Medications to reduce the abnormal
  immune response (see medication section)
• Radiation therapy to destroy areas of
  affected lymph nodes that cannot be removed surgically

What medications treat Castleman disease?

Several different classes of medications have been used to treat Castleman
disease.

• Corticosteroid drugs suppress the immune response. They can be useful in
  people with immune system disorders and some cancers. These drugs may be given alone,
  or sometimes in combination with the type of chemotherapy drugs used to treat
  cancers.
• These chemotherapy drugs are most often used in Castleman disease
• Chemotherapy and corticosteroids may also be combined with radiation therapy
  to destroy the abnormal tissue.
• Immunotherapy involves administering drugs that boost or strengthen the
  body’s natural immune response. Immunotherapy drugs include
  • siltuximab (Sylvant),
    a monoclonal antibody drug that binds to IL-6.
  • Rituximab (Rituxan) is a monoclonal antibody often used to treat lymphoma that
    is also sometimes used to treat Castleman disease.
  • 
    
    Tocilizumab (Actemra) is an
    IL-6 receptor antagonist antibody that also has been used.
• Immunomodulating
  drugs such as thalidomide (Thalomid) and lenalidomide (Revlimid)
  are used to treat multiple myeloma and some lymphomas, and also
  can be helpful for some
  people with Castleman disease.
• 
  Interferon-alfa (a man-made version of an
  immune-boosting substance produced by the body) is occasionally used to treat
  Castleman disease.
• Anti-viral medications such as ganciclovir, valganciclovir, and
  foscarnet have been successfully used to treat multicentric Castleman disease
  associated with infection with the virus HHV-8.

Is there surgery to treat Castleman disease?

Surgical removal of the involved lymph nodes is a helpful way to treat
unicentric (localized) Castleman disease. Surgery also may be used in multicentric Castleman disease as a way to control symptoms, although in
multicentric Castleman disease, it is not typically possible to remove all of
the affected lymph nodes.

Which specialties of health care professionals treat Castleman disease?

A number of different specialists may be involved in the care of a patient
with Castleman disease, depending upon the type and extent of the disease,
including hematologist-oncologists, radiation therapy specialists, and surgeons.
If the patient has HIV-associated Castleman disease, infectious disease
specialists will also likely be involved in the patient’s care.

What questions should I ask the doctor about Castleman disease?

Questions to ask the doctor about Castleman disease include the following:

1. What type of Castleman disease do I have?
2. How was the diagnosis established? Was my biopsy
   read by a pathologist who is an expert on Castleman disease? If not, should I
   have a second opinion?
3. What additional tests, if any, do I need?
4. Do you have experience treating patients with
   Castleman disease? Should I get a second opinion from another physicians
   regarding treatment options?
5. What are all the treatment options, and which do
   you recommend?
6. What are the side effects of treatment, and how
   will treatment affect my daily life?
7. What is the likelihood that the treatment will be
   successful? If the disease returns after treatment, what are my options?
8. What is my prognosis, or outlook for survival?
9. What kind of follow-up care will be required after
   treatment?
10. Am I eligible for any clinical trials or new treatments?

What is the life expectancy and prognosis for a person with Castleman
disease?

It is difficult to determine the outlook for any given individual with
Castleman disease because the condition takes different forms and is very rare.
Estimates of 3-year survival rates are based on whether the affected person is
also infected with HIV and upon certain characteristics of the lymph nodes when
observed under the microscope. For example, in a group of patients with
unicentric Castleman disease who had certain microscopic features in their lymph
nodes, 93% were alive 3 years after the diagnosis. In HIV+ patients with
multicentric disease, only 28% were alive after 3 years. It is important to note
that these survival statistics were based upon a small number of patients who
were treated in the past, and treatments are always improving.