Castleman Disease

What is Castleman disease?

Castleman disease is a rare disorder in which the lymph nodes and related immune tissue grow abnormally. Lymph nodes are small, bean-shaped glands found throughout the body that filter fluid and help fight infection. In Castleman disease, one or more of these nodes becomes enlarged because certain immune cells multiply more than they should. The condition is not classified as a cancer, but it is sometimes described as a lymphoproliferative disorder, meaning a condition in which lymphocytes (a type of white blood cell) grow in an uncontrolled way. In some forms it can behave aggressively and needs specialist care.

Doctors usually divide Castleman disease into two main groups:

• Unicentric Castleman disease (UCD): only one lymph node or one group of nodes in a single area of the body is affected. This is the more common and generally the milder form.
• Multicentric Castleman disease (MCD): enlarged lymph nodes appear in several regions of the body, and the whole body is often affected by inflammation. MCD is further divided into a form linked to a virus called human herpesvirus 8 (HHV-8), a form associated with a condition called POEMS syndrome, and a form with no identified cause, known as idiopathic multicentric Castleman disease (iMCD).

Castleman disease can occur at any age. Unicentric disease is often found in young adults, while multicentric disease tends to be diagnosed later in adulthood, although children can also be affected. It occurs in both men and women. Because it is rare, many people have never heard of it before their own diagnosis, and it is often first suspected when an enlarged lymph node is found during evaluation for another problem.

Castleman disease symptoms

Castleman disease symptoms vary a great deal depending on the type. Some people have no symptoms at all, while others feel very unwell. The following are the features that doctors most often see:

• A painless swelling or lump, most often in the neck, armpit, chest, abdomen or groin
• Fever that comes and goes without an obvious infection
• Night sweats
• Unintended weight loss
• Persistent tiredness or weakness
• Loss of appetite or feeling full quickly
• Enlarged liver or spleen, which may cause fullness or discomfort in the abdomen
• Fluid buildup in the legs, abdomen or around the lungs
• Skin changes such as rashes or small red spots
• Nerve symptoms such as numbness or tingling in the hands and feet

In unicentric Castleman disease, many people have no symptoms and the enlarged node is found by chance on a scan. When symptoms do occur, they usually come from the mass pressing on nearby structures. For example, a node in the chest may cause a cough, chest discomfort or breathlessness, and a node in the abdomen may cause pain or a sense of pressure.

In multicentric Castleman disease, symptoms are usually more widespread because the body is producing excess inflammatory chemicals, particularly a signaling protein called interleukin-6 (IL-6). This can cause flu-like illness, fevers, drenching sweats, marked fatigue and weight loss. Blood tests often show anemia (a low red blood cell count), low platelets, abnormal kidney function and high levels of inflammation markers. A severe subtype of iMCD, sometimes called TAFRO syndrome, is characterized by low platelets, fluid retention, fever, bone marrow changes and kidney problems, and can develop quickly.

Symptoms may appear gradually over months or arrive suddenly. Because they overlap with many other conditions, including infections, autoimmune diseases and lymphoma (a cancer of the lymphatic system), Castleman disease is often diagnosed only after other explanations have been considered.

Causes and risk factors

The exact Castleman disease causes are not fully understood, and they appear to differ between the types.

• Excess interleukin-6 (IL-6): in most forms, especially multicentric disease, the body produces too much IL-6 and related inflammatory signals. IL-6 normally helps coordinate the immune response, but in excess it drives lymph node growth, fever, anemia and other symptoms.
• Human herpesvirus 8 (HHV-8): this virus, also known as Kaposi sarcoma-associated herpesvirus, is found in a subset of multicentric cases. Infected cells within the lymph nodes make a viral form of IL-6, which fuels the disease.
• HIV infection: people living with HIV have a higher chance of developing HHV-8-associated multicentric Castleman disease, because a weakened immune system allows HHV-8 to become active.
• POEMS syndrome: a rare disorder of plasma cells (antibody-producing cells) that causes nerve damage, organ enlargement, hormone changes and skin changes. Castleman disease is one of its recognized features.
• Unknown factors: in idiopathic multicentric Castleman disease and in most unicentric cases, no cause is found. Researchers are studying possible roles for genetic changes in the abnormal cells, autoimmune processes and undiscovered infections.

Castleman disease is not considered inherited, and it does not pass from parent to child in a predictable way. It is also not contagious, although HHV-8 itself is a virus that can spread between people. There is currently no evidence that diet, lifestyle or environmental exposures cause the condition, and having Castleman disease is not the result of anything a person did or failed to do.

Known risk factors are limited. Living with HIV or another cause of a weakened immune system raises the risk of the HHV-8-associated form. Age and sex patterns exist, with unicentric disease more frequent in younger adults and multicentric disease more frequent in middle age and older, but the condition can affect anyone.

Castleman disease diagnosis

Castleman disease diagnosis requires a combination of tissue examination, blood tests and imaging. There is no single test that confirms the condition on its own, and because it looks similar to other disorders, doctors follow a careful step-by-step approach.

• Physical examination and history: your doctor will ask about symptoms such as fever, sweats, weight loss and swelling, and will examine the neck, armpits, groin and abdomen for enlarged nodes or organs.
• Blood tests: a complete blood count checks for anemia and low platelets. Other tests look at kidney and liver function, protein levels such as albumin, immune proteins (immunoglobulins) and inflammation markers such as C-reactive protein. Testing for HIV and HHV-8 is usually performed because these change the type of disease and its treatment.
• Imaging: a computed tomography (CT) scan, which uses X-rays to create detailed cross-sectional pictures, or a positron emission tomography (PET) scan, which highlights areas of high cell activity, helps show how many lymph node regions are involved. This is essential for distinguishing unicentric from multicentric disease.
• Lymph node biopsy: this is the key test. A surgeon removes an entire enlarged lymph node, or a large portion of it, so that a pathologist (a doctor who examines tissue under a microscope) can study its structure. A needle biopsy alone is often not enough, because the diagnosis depends on seeing the overall pattern of the node. The pathologist looks for specific features and may describe the tissue as hyaline vascular, plasma cell or mixed type.
• Special tissue tests: staining for HHV-8 within the node helps identify the virus-associated form. Other tests rule out lymphoma and related cancers.
• Bone marrow examination: in multicentric disease, a sample of bone marrow may be taken to assess blood cell production and to exclude other conditions.

For idiopathic multicentric Castleman disease, international consensus criteria have been developed. In general terms, these require typical findings on a lymph node biopsy, enlarged nodes in more than one region, a combination of clinical and laboratory abnormalities, and the exclusion of infections, autoimmune diseases and cancers that can mimic the condition. Because the picture is complex, the diagnosis is usually made by a hematologist (a doctor who specializes in blood and lymphatic disorders) working closely with a pathologist. At Acibadem hospitals, this evaluation is coordinated through the Hematology Department together with radiology and pathology teams.

Castleman disease treatment options

Castleman disease treatment depends mainly on the type, how severe the symptoms are, and whether HHV-8 or HIV is present. Care is individualized, and your doctor may combine several approaches over time.

Treatment for unicentric Castleman disease

• Surgery: removing the affected lymph node or node group is the standard approach. In many cases, complete surgical removal resolves the disease, and symptoms caused by pressure on nearby structures often improve afterward. Long-term follow-up is still recommended to check for any return.
• Radiation therapy: when the node is in a location where surgery would be risky, targeted radiation may be used to shrink it.
• Embolization: a procedure that blocks the blood supply to the mass may be used before surgery to reduce bleeding, or as an alternative in selected cases.
• Medication: if the mass cannot be removed and is causing symptoms, drugs used for multicentric disease may be considered.

Treatment for HHV-8-associated multicentric Castleman disease

• Rituximab: a monoclonal antibody (a laboratory-made protein that targets a specific marker) directed against B cells, the type of lymphocyte affected. It is commonly used and is often effective in this form.
• Antiviral therapy: people who also have HIV are treated with antiretroviral medication to strengthen the immune system. Antiviral drugs directed at HHV-8 may be added in some situations.
• Chemotherapy: in aggressive disease, chemotherapy drugs may be combined with rituximab.

Treatment for idiopathic multicentric Castleman disease

• Siltuximab: a monoclonal antibody that blocks IL-6 directly. It is approved specifically for iMCD and is often the first choice. It is given by intravenous infusion, usually on a continuing schedule, because stopping it may allow symptoms to return.
• Tocilizumab: another antibody that blocks the receptor for IL-6, used where siltuximab is unavailable or not suitable.
• Corticosteroids: anti-inflammatory steroid medicines such as prednisone are frequently used to control symptoms quickly, especially at the start of treatment or during flares. They are usually reduced over time because of side effects with long-term use.
• Rituximab: may be used when IL-6-blocking drugs do not work well enough.
• Immune-modulating and chemotherapy drugs: in severe or life-threatening disease, doctors may use combination chemotherapy or other immune-suppressing medicines. Some newer targeted agents are being studied in clinical trials.

Supportive care

Alongside disease-directed treatment, supportive care addresses complications. This may include blood transfusions for severe anemia, treatment for kidney problems, drainage of fluid collections, and management of infections. Some people who have had prolonged illness or a hospital stay benefit from physical rehabilitation to rebuild strength. Regular blood tests and scans monitor how the disease responds, and the plan is adjusted if the response is incomplete.

Living with Castleman disease and outlook

The outlook for Castleman disease varies widely by type. For unicentric disease, the prognosis is generally favorable, and most people do well after surgical removal. Recurrence is uncommon but possible, so follow-up visits continue for several years.

Multicentric Castleman disease is a more serious, often long-term condition. Modern treatments that block IL-6 or target B cells have improved outcomes considerably compared with the past, and many people achieve good control of symptoms. However, the disease can relapse, some people need ongoing treatment for years, and severe forms such as TAFRO syndrome can progress rapidly and require intensive care. People with HHV-8-associated disease have a higher chance of developing certain related conditions, such as Kaposi sarcoma or lymphoma, and are monitored for these.

Living with the condition often means regular appointments, blood tests and infusions. Fatigue can be a lasting problem even when the disease is controlled. Practical steps that many patients find helpful include keeping a symptom diary, taking medicines exactly as prescribed, staying up to date with recommended vaccinations after discussing them with the care team (some vaccines are not suitable during certain treatments), and reporting new symptoms early. Because the disease is rare, connecting with patient organizations and registries can provide information and a sense of community, and participation in research may be an option for some.

Emotional effects are common after a rare diagnosis. Anxiety about relapse, uncertainty about the future and the strain of ongoing treatment are all normal reactions, and psychological support is a recognized part of care.

Frequently asked questions

Is Castleman disease a cancer?

Castleman disease is not classified as a cancer. It is a lymphoproliferative disorder, meaning that immune cells in the lymph nodes grow excessively, but the cells do not have the features of malignancy. However, some forms behave aggressively, and people with multicentric disease, particularly the HHV-8-associated type, have a higher risk of developing lymphoma or Kaposi sarcoma, so ongoing monitoring is important.

What are the first Castleman disease symptoms people notice?

In unicentric disease, the first sign is often a painless lump or a mass found incidentally on a scan, with no other symptoms. In multicentric disease, early symptoms are frequently general and flu-like, such as fever, night sweats, tiredness and weight loss, along with swollen nodes in more than one area. Because these symptoms are nonspecific, the diagnosis is often delayed while other causes are ruled out.

What causes Castleman disease?

The causes are only partly understood. In many cases the disease is driven by excess production of the inflammatory protein interleukin-6. In some multicentric cases, infection with human herpesvirus 8 is responsible, especially in people with HIV. A minority of cases are linked to POEMS syndrome. In idiopathic multicentric and most unicentric cases, no cause has been identified, and research into genetic and immune factors is ongoing.

How is Castleman disease diagnosed?

Diagnosis rests on examining tissue from an enlarged lymph node, usually removed whole by a surgeon, under the microscope. Blood tests assess inflammation, blood counts, kidney function and the presence of HIV or HHV-8. CT or PET scans show how many regions are involved. Doctors also perform tests to exclude lymphoma, infections and autoimmune diseases, since these can look very similar. For idiopathic multicentric disease, published consensus criteria guide the final decision.

Can Castleman disease be cured?

Unicentric Castleman disease is often cured by complete surgical removal of the affected node, although follow-up continues in case of recurrence. Multicentric disease is generally considered a long-term condition rather than one that is cured. Treatments such as siltuximab, tocilizumab and rituximab can control it well in many people, and some achieve long periods without symptoms, but relapse is possible and continuing treatment may be needed.

What is the most common Castleman disease treatment?

For unicentric disease, surgery is the standard treatment. For idiopathic multicentric disease, siltuximab, a medicine that blocks interleukin-6, is usually recommended first, often with corticosteroids for rapid symptom control. For HHV-8-associated disease, rituximab is commonly used, together with antiretroviral therapy in people with HIV. The choice depends on the type, severity and individual health factors, and your doctor may adjust the plan based on response.

Is Castleman disease hereditary or contagious?

Castleman disease is not known to be inherited, and it is not considered contagious. Family members are not at increased risk simply because a relative has the condition. The HHV-8 virus associated with one form can be transmitted between people, but most people who carry the virus never develop Castleman disease, and the disease itself does not spread from person to person.

When to see a doctor

Anyone who notices a persistent swollen lymph node, especially one that is growing, lasts more than a few weeks, or is accompanied by fever, night sweats or unexplained weight loss, should be evaluated by a doctor. People already diagnosed with Castleman disease should report new or worsening symptoms promptly, since flares can develop quickly.

Seek urgent medical attention if you experience any of the following:

• Difficulty breathing, chest pain or a rapidly worsening cough
• High or persistent fever, particularly while taking treatments that lower immunity
• Sudden swelling of the abdomen, legs or face, or a rapid gain in body weight from fluid
• Passing very little urine, or signs of kidney problems such as marked ankle swelling and confusion
• Unusual bleeding or bruising, blood in the urine or stool, or tiny red spots on the skin
• Severe weakness, dizziness or fainting
• Confusion, severe headache or new numbness and weakness in the limbs
• Signs of a serious infection, such as chills, rapid heartbeat or feeling very unwell

These signs may indicate a serious flare, a complication such as kidney failure or fluid around the lungs, or an infection that needs immediate treatment. Early assessment allows problems to be addressed before they become life-threatening.