Castleman Disease

Castleman disease is a rare group of conditions affecting lymph nodes. Lymph nodes are small, bean-shaped structures throughout the body that help fight infection. In Castleman disease, these nodes swell (enlarge). This swelling, along with a range of other symptoms, defines the disease.

The most common type, called unicentric Castleman disease (UCD), involves a single swollen lymph node, usually in the chest or neck, but sometimes elsewhere.

A more complex type is multicentric Castleman disease (MCD). This form features multiple swollen lymph nodes, along with inflammation and potential problems with organs like the heart, kidneys, or liver. There are three main subtypes of MCD:

• HHV-8-associated MCD: This type is linked to a virus called human herpesvirus-8 (HHV-8) and is sometimes seen in people with HIV (human immunodeficiency virus).

• Idiopathic MCD (HHV-8-negative MCD): This type has no known cause. It's often called "idiopathic" because its origin is unknown. A severe form of idiopathic MCD is iMCD-TAFRO. This name comes from the symptoms, often including inflammation (T), blood clots (A), and an abnormally low number of red blood cells (F).

• POEMS-associated MCD: This type is connected to a rare blood disorder called POEMS syndrome. POEMS syndrome damages nerves and affects various parts of the body.

Sometimes, a person might have a few swollen lymph nodes and mild symptoms, but not enough to meet the full criteria for MCD. In these cases, the person might have another illness, or they might have a recently identified form of Castleman disease called oligocentric Castleman disease. This form is also rare.

Treatment and the outlook for Castleman disease depend on the specific type. UCD, with just one swollen lymph node, is often successfully treated with surgery. The best approach for oligocentric Castleman disease, involving a small number of enlarged lymph nodes and mild symptoms, isn't fully established, but is likely similar to the treatment for UCD.

Not everyone with MCD responds to the first treatment. For HHV-8-associated MCD and idiopathic MCD, there are medications that can sometimes help. Ongoing research is critical to improving treatments and understanding this complex disease.

Castleman disease is a condition affecting lymph nodes. Sometimes, the disease is only in one area (unicentric), and other times, it affects many areas (multicentric).

Unicentric Castleman Disease: Many people with unicentric Castleman disease don't have any noticeable symptoms. A doctor might find an enlarged lymph node during a routine checkup or while testing for something else. Occasionally, people with unicentric disease do experience some of the symptoms listed below, which are also seen in multicentric disease.

Possible Symptoms (Unicentric and Multicentric):

• Fever: A persistent feeling of warmth.
• Unexplained Weight Loss: Losing weight without trying to.
• Fatigue: Feeling very tired all the time.
• Night Sweats: Sweating heavily at night.
• Swelling: Fluid buildup in the body.
• Enlarged Liver or Spleen: These organs can become larger than usual.
• Anemia: A low red blood cell count, making you feel weak and tired.
• Low or High Platelet Counts: Platelets help blood clot. Having too few or too many can be a sign of a problem.
• Kidney Issues: Higher-than-normal creatinine levels show the kidneys aren't working as well as they should.
• High or Low Levels of Immunoglobulins (Antibodies): Immunoglobulins fight infection. Unusual levels can indicate a problem.
• Low Albumin Levels: Albumin is a blood protein. Low levels can cause swelling.

A More Serious Form (iMCD-TAFRO): This is a more severe type of multicentric Castleman disease. Symptoms include:

• Low Platelet Count (Thrombocytopenia): This makes it harder for the blood to clot.
• Anasarca (Severe Swelling): Widespread fluid buildup throughout the body.
• Fever or Elevated C-Reactive Protein (CRP): CRP is a marker for inflammation.
• Reticulin Fibrosis: This is a change in the structure of bone marrow, which can be detected by a bone marrow biopsy.
• Organ Swelling (Organomegaly): The liver, spleen, or other organs might swell.

When to See a Doctor:

If you notice a swollen lymph node in your neck, armpit, collarbone, or groin, or if you experience persistent feelings of fullness in your chest or abdomen, fever, fatigue, or unexplained weight loss, it's important to talk to your doctor. Early diagnosis and treatment are key to managing Castleman disease.

If you notice a swollen lump in your neck, armpit, collarbone, or groin, it's important to see your doctor. Similarly, unexplained persistent feelings of fullness in your chest or belly, fever, tiredness, or weight loss should also prompt a call to your healthcare provider. These symptoms could be signs of something more serious that needs medical attention.

Understanding Castleman disease can be tricky. We don't know exactly what causes the unicentric form, or the more widespread idiopathic multicentric Castleman disease (MCD). However, a type of MCD linked to a virus called HHV-8 is more common in people whose immune systems aren't working properly. This might happen if they have HIV or another condition that weakens their immune response.

Castleman disease can happen to anyone, regardless of age or sex. Most people are diagnosed with it during their middle years, but it can develop at any time, even in childhood.

We don't know what causes unicentric Castleman disease or idiopathic multicentric Castleman disease. However, having a weakened immune system, like from an infection with HIV, or having a condition that makes your immune system less effective, can increase the chances of getting HHV-8-positive multicentric Castleman disease. This means the immune system isn't working properly and is more vulnerable to this type of Castleman disease.

Castleman disease, a condition affecting lymph nodes, generally has a good outcome when the affected lymph node is removed. People with this type, called unicentric Castleman disease (UCD), usually don't see a change in their life expectancy. However, there's a small but important risk of developing a rare autoimmune disease called paraneoplastic pemphigus. This condition causes painful blisters in the mouth and on the skin, which can sometimes be mistaken for other illnesses. Even though the chance of getting paraneoplastic pemphigus is relatively low, it's crucial to be checked for it if you have UCD. Regular checkups are vital to catch any signs early.

A different type of Castleman disease, called idiopathic multicentric Castleman disease, can progress quickly and cause serious problems with organs. These problems can become life-threatening, requiring intensive medical care. This may include using a ventilator to help with breathing, along with treatments like dialysis (to filter waste from the blood) and transfusions (to replace lost blood components). These treatments support organ function during a critical period.

Another type, HHV-8-positive multicentric Castleman disease, can lead to life-threatening infections and organ failure. For people who also have HIV/AIDS, the outcome tends to be significantly worse. This combination of conditions presents a more complex and challenging medical situation.

Your doctor will likely recommend some tests to help figure out if you have Castleman disease. First, they'll review your medical records and do a thorough physical exam. Then, they might suggest:

• Blood and urine tests: These tests are used to look for other infections or medical problems. They can also check for anemia (low red blood cells) and changes in blood proteins, which can sometimes be signs of Castleman disease.

• Imaging tests: These tests help find any enlarged lymph nodes, liver, or spleen, which are common in Castleman disease. A common imaging test is a CT scan (computed tomography scan) of your neck, chest, belly (abdomen), and pelvis. Sometimes, a PET scan (positron emission tomography scan) is used. A PET scan can help doctors see if Castleman disease is present and if treatment is working. It does this by showing how different parts of your body use energy.

• Lymph node biopsy: This is a very important test for diagnosing Castleman disease and making sure it's not something else, like lymphoma. A biopsy involves taking a small piece of tissue from an enlarged lymph node. This tissue sample is then examined under a microscope in a lab to look for specific signs of Castleman disease.

Castleman disease treatment varies depending on the type.

Unicentric Castleman Disease (UCD): The standard treatment for UCD is surgery to remove the swollen lymph node. This is often a significant operation, especially if the affected lymph node is located in the chest or belly. In most cases, surgery successfully cures UCD, but sometimes the disease returns. If surgery isn't an option, doctors might use medicines typically used for multicentric Castleman disease. If medicines don't work, radiation therapy could be considered. More research is needed for a specific treatment approach for a similar condition called oligocentric Castleman disease, but the treatment usually mirrors that of UCD. Regular checkups, including scans and blood tests, are important to monitor for any recurrence.

HHV-8-positive Multicentric Castleman Disease (MCD): The first treatment for this type is usually a medicine called rituximab. It's generally quite effective, but sometimes additional medicines like antiviral drugs or chemotherapy are needed. Antiviral medicines stop the activity of the virus HHV-8 or HIV. Chemotherapy helps reduce the number of extra immune cells.

Idiopathic Multicentric Castleman Disease (MCD): The usual first treatment for this type is siltuximab. In the US, it's the only medicine specifically approved for this type of MCD. Many people who respond well to siltuximab have long-term success. This medicine blocks a protein called interleukin-6, which is produced in excess in people with this disease. For seriously ill patients, corticosteroids (like prednisone) might be given to manage inflammation. Chemotherapy may also be needed to help control immune system activity. If siltuximab doesn't work, other treatments like rituximab or sirolimus could be used.

Important Note: This information is for general knowledge and does not constitute medical advice. Always consult with a healthcare professional for diagnosis and treatment options.