Multicentric Castleman Disease

In about half of people with multicentric Castleman disease (MCD), it is caused by human herpesvirus-8 (HHV-8), in which case it is called HHV-8-associated MCD. This type of MCD usually occurs in people with human immunodeficiency virus (HIV) or a weakened immune system due to other reasons, because the weakened immune system is not able to manage a HHV-8 infection. It is thought that the infection multiplies in the lymph nodes, leading to the release of high levels of inflammatory chemicals (particularly cytokines such as interleukin-6), causing the specific symptoms of MCD.

In the remaining half of cases of MCD, the cause is not known, in which case it is called HHV-8 negative MCD, or idiopathic MCD (iMCD). Possible factors that have been speculated to play a role in causing iMCD include being infected with a virus other than HHV-8, acquiring a genetic mutation that signals the release of substances that lead to the disease, inheriting a genetic mutation that predisposes a person to developing the disease, and autoimmunity (when the body's immune system mistakenly attacks healthy tissues). People with iMCD often also have high levels of cytokines, but the cause of their increased production in iMCD is not yet known.

The signs and symptoms of multicentric Castleman disease (MCD) are often nonspecific and blamed on other, more common conditions. However, if MCD is suspected, the following tests may be recommended to help establish the diagnosis and rule out other conditions that cause similar features:

• Blood tests can be ordered to evaluate the levels of Interleukin-6 (IL-6) and other substances in the body, which can be elevated in people with MCD. They can also be helpful in ruling out other autoimmune conditions and infections that are associated with similar signs and symptoms
• Imaging studies (such as a CT scan, PET scan, MRI scan, and/or ultrasound) can help identify enlarged lymph node(s) and other health problems
• A biopsy of affected tissue, often a lymph node, is usually recommended to confirm the diagnosis

To our knowledge, there is no evidence that multicentric Castleman disease is an inherited disease.

The long-term outlook (prognosis) for people with multicentric Castleman disease (MCD) varies. In some cases, the condition may persist for several months or years without progressing (worsening overtime). Other people affected by MCD experience episodes of severe symptoms that may improve spontaneously or in response to treatment, only to recur at a later date. People with MCD who are also HIV- positive may be at an elevated risk for a severe form that is rapidly progressive and can lead to death within weeks.

In general, the prognosis is worse in affected people who do not receive appropriate treatment and in those with HIV-associated MCD.

Treatment of multicentric Castleman disease (MCD) is challenging, and no single treatment works for all people with the disease. Treatment options may depend on the type of MCD (HHV-8-associated or idiopathic) as well as the severity of symptoms.

HHV-8-associated MCD is typically initially treated with rituximab to fight against immune cells called B lymphocytes. This treatment is reportedly highly effective for HHV-8-associated MCD. Antiviral medications (particularly for those with HIV) and/or chemotherapy may also be recommended.

Idiopathic MCD (iMCD) is typically initially treated with siltuximab or tocilizumab (which aim to control activity of interleukin-6) with or without corticosteroids. Unfortunately, about half of people do not improve with these therapies. In those with only mild symptoms, rituximab may be an alternative option for initial treatment. In very severe cases, adjuvant combination chemotherapy is also recommended. Other types of therapies may be recommended if the above therapies are not effective.