Castleman disease (CD) can be difficult to diagnose as it is both a rare disease and an imitator of many other diseases. Patients can have the same symptoms as some cancers and some autoimmune diseases. Due to the complexity of the disease, physicians often need to rule out many other diseases before CD is suspected.
There are various types of Castleman disease and they have very important differences in symptoms, disease course, and treatment. However, they all share specific changes to the lymph nodes that must be observed through a microscope. Therefore, patients must undergo an excisional lymph node biopsy to be diagnosed with CD. This is absolutely necessary so that patients with other diseases are not incorrectly diagnosed with Castleman disease.
The treatment options for Castleman disease are specific to the subtype diagnosed by your physician.
Unicentric Castleman disease (UCD): Surgery is considered by experts to be the first-line treatment for almost all cases of UCD. A patient is considered cured of UCD if their enlarged lymph node or nodes are removed completely and any previous clinical/laboratory abnormalities return to normal. Sometimes, removing the enlarged lymph node(s) is not possible. In these cases, medications or radiation may be administered to attempt to shrink the enlarged lymph node. Some UCD patients may experience inflammatory symptoms (fever, fatigue) and elevated inflammatory laboratory markers after lymph node excision. These patients are sometimes treated with treatments frequently used to treat MCD. There are no reported cases of UCD transforming into MCD. Your medical team will discuss the options and risk for surgery depending on the location of the enlarged lymph nodes. More information on the current treatment guidelines can be found here.
HHV-8 associated Multicentric Castleman disease (HHV-8 associated MCD): Rituximab is highly effective in treating HHV-8 associated MCD. This drug is highly specific to B cells, a special type of immune cell. This is a fortunate advantage of rituximab, as traditional chemotherapy drugs are not specific and therefore result in different side effects. The degree of immunosuppression is also milder than traditional chemotherapy drugs. Your medical team will discuss the side effects you can expect from rituximab. Further information can be found here.
HHV-8 negative/idiopathic Multicentric Castleman disease (iMCD): A few specific therapies such as siltuximab and tocilizumab are considered first-line treatment. These drugs target a specific compound (interleukin-6) that is highly involved in inflammation. Unlike traditional chemotherapy, anti-IL6 therapy is more specific so the side effects are milder. The amount of immunosuppression will be dependent on whether other drugs are used simultaneously. For reasons still unknown, Rituximab tends to not work as successfully in iMCD patients compared to HHV-8 associated MCD patients.
Unfortunately, the anti-IL6 therapy is not effective in all patients. Sometimes, rituximab or chemotherapy regimens used for blood cancers are used if a patient does not improve with anti-IL6 therapy. More information on the current treatment guidelines can be found here. The side effects will be very specific to the treatment chosen by the medical team.
The good news is that in the last decade, an explosion in Castleman disease research has identified new targets and there is hope new treatments will emerge soon.
A new clinical trial for the medication sirolimus for iMCD patients who did not improve on siltuximab or tocilizumab was opened in the USA in 2019. Patients can learn more about this trial at cdcn.org/trial. The trial has been posted to the federal registry for all clinical trials here.