Castleman disease

Overview

Castleman disease is a group of rare conditions that cause enlarged lymph nodes and a wide range of symptoms. The most common type affects a single lymph node, usually in the chest or neck. But it can occur in other areas. This form of the disease is called unicentric Castleman disease (UCD).

Multicentric Castleman disease (MCD) involves multiple regions of enlarged lymph nodes. It can cause inflammatory symptoms and issues with organ function. There are three types of MCD:

• HHV-8/KSHV-associated MCD. This type is linked to human herpesvirus type 8 (HHV-8), also called Kaposi's sarcoma-associated herpesvirus (KSHV). It often occurs in people with human immunodeficiency virus (HIV) or other causes of immune deficiency.
• Idiopathic MCD. The cause of this type is unknown. It is also called HHV-8-negative MCD. The most serious form of this type of MCD is known as iMCD-TAFRO. The name TAFRO comes from the first letter of its main symptoms. Thrombocytopenia is a low platelet count. Anasarca is swelling and fluid in the body. Fever or a higher level of C-reactive protein is a marker of inflammation. Reticulin fibrosis/renal dysfunction is scarring of the bone marrow and decreased function of kidneys. Organomegaly is organ swelling.
• POEMS-associated MCD. This type is linked to another condition called POEMS syndrome. POEMS syndrome is a rare blood condition that damages nerves and affects other parts of the body. The name POEMS comes from the first letter of its main symptoms. Polyneuropathy is numbness, tingling and weakness in the legs or hands caused by nerve damage. Organomegaly is an enlarged spleen, liver or lymph nodes. Endocrinopathy is atypical hormone levels. Monoclonal protein is a protein made by atypical plasma cells in bone marrow make. Skin changes may include a change in color and thickness or increased hair growth.

Sometimes, people may have 2 to 3 enlarged lymph nodes and mild symptoms that do not meet the standards used to diagnose for MCD. These people may have another disease, or they may have the recently described subtype of Castleman disease called oligocentric. This also is known as regional Castleman disease. This subtype is rare.

Treatment and outlook vary depending on the type of Castleman disease you have. Unicentric Castleman disease, which involves only one enlarged lymph node, can usually be successfully treated with surgery.

The best treatment for oligocentric Castleman disease, which involves a few enlarged lymph nodes and has limited symptoms, is not known. But it is thought to be similar to the treatment for unicentric Castleman disease.

Not all people with MCD respond to the first treatment. But medicines are available that can help treat HHV-8-associated MCD and idiopathic MCD.

Symptoms

Many people with unicentric Castleman disease don't notice any signs or symptoms. The enlarged lymph node may be found during a physical exam or an imaging test for a different issue.

Some people with unicentric Castleman disease might have signs and symptoms that are more often seen in multicentric Castleman disease. These may include:

Body symptoms

These symptoms may include:

• Fever.
• Weight loss that happens without trying.
• Fatigue.
• Night sweats.
• Swelling.
• Enlarged liver or spleen.

Blood test findings

Lab test results may include:

• Low red blood cell count, also called anemia.
• High or low platelet counts.
• Higher creatinine levels that happen because the kidneys don't work properly.
• Higher levels of antibodies known as immunoglobulins.
• Low levels of albumin, a blood protein.

Symptoms of the more serious form of idiopathic MCD called iMCD-TAFRO are:

• Low platelet count, also called thrombocytopenia.
• Swelling and fluid in the body, known as anasarca.
• Fever or a higher level of C-reactive protein, a marker of inflammation.
• Reticulin fibrosis, which is a scarring of the bone marrow and checked by taking a sample of bone marrow.
• Renal dysfunction. The R also stands for decreased function of kidneys.
• Organ swelling, also called organomegaly.

When to see a doctor

If you notice an enlarged lymph node on the side of your neck or in your underarm, collarbone or groin area, talk with your healthcare professional. Also call your care team if you have a lasting sense of fullness in your chest or abdomen, fever, fatigue, or weight loss that you can't explain.

Causes

It's not clear what causes unicentric Castleman disease or idiopathic multicentric Castleman disease (MCD). But HHV-8-positive MCD is known to occur in people whose immune systems are weakened, including people with HIV.

Risk factors

Castleman disease can affect people of any age. People usually are diagnosed with Castleman disease during midlife, but it can happen at any age, including during childhood.

There are no known risk factors for unicentric Castleman disease or idiopathic multicentric Castleman disease. Infection with HIV or having a condition that decreases how well the immune system works raises the risk of having HHV-8-positive multicentric Castleman disease.

Complications

People with unicentric Castleman disease (UCD) usually do well once the affected lymph node is removed, and life expectancy is usually not changed. But people with this condition are at increased risk of developing a rare autoimmune condition called paraneoplastic pemphigus. This condition can be life-threatening. Paraneoplastic pemphigus causes blisters in the mouth and on the skin that are often misdiagnosed. Though the risk of developing paraneoplastic pemphigus is low, being checked for this condition is important if you have UCD.

Idiopathic multicentric Castleman disease can rapidly get worse and involve life-threatening issues with organ function. This requires critical care with a machine that helps with breathing, called a ventilator, and treatments that help with organ function, such as dialysis and transfusions.

HHV-8-positive multicentric Castleman disease may involve life-threatening infections and organ failure. People who also have HIV/AIDS can have worse outcomes.