Frequently Asked Questions
- What is Castleman disease?
- How is Castleman disease diagnosed?
- What are the different types of Castleman disease?
- What are the symptoms of Castleman disease?
- What causes Castleman disease? Who is at risk?
- Are there any clinical trials for Castleman disease?
- Is Castleman disease a form of cancer or does it cause cancer?
- Is it safe for me to get pregnant?
- What is the CDCN doing to combat Castleman disease?
- How can I help accelerate finding a cure for Castleman disease?
- Does Dr. David Fajgenbaum treat patients at the University of Pennsylvania?
What is Castleman disease?
Castleman disease is a group of rare disorders characterized by lymph node enlargement, specific microscopic changes to the lymph nodes, and a broad range of symptoms and laboratory findings. The lymph nodes and the cells that reside in them (lymphocytes) are an integral part of our immune system that help us fight invading organisms. For reasons unknown, these lymph nodes undergo transformations that result in overproduction of lymphocytes and other inflammatory compounds. The overproduction leads to lymph node enlargement and possible organ dysfunction.
How is Castleman disease diagnosed?
Diagnosis of CD is difficult because its symptoms are similar to those of other diseases. Enlargement of lymph nodes and the symptoms caused by uncontrolled inflammation can occur in other diseases. Diagnosis of CD requires biopsy of an enlarged lymph node and analysis by a pathologist. The pathologist will use a light microscope and search for specific features. The biopsy and pathology analysis requirements are important to prevent misdiagnosis of CD in patients with other diseases.
What are the different types of Castleman disease?
Although the subtypes of Castleman disease all share common features in the lymph nodes, when viewed under the microscope, the subtypes can differ greatly in symptoms, treatment, and disease course. The two main subtypes are Unicentric Castleman disease (UCD) and Multicentric Castleman disease (MCD).
Unicentric Castleman disease (UCD) involves a single enlarged lymph node (or single region of enlarged lymph nodes) and typically presents with discomfort associated with the enlarged lymph node but can occasionally involve some systemic MCD-like symptoms (see below). Surgical removal of the enlarged node usually eliminates CD from the patient resulting in no further complications or relapses. However, a minority of patients will not have a complete resolution of symptoms. There are no known cases reported of UCD becoming or transitioning into MCD.
Multicentric Castleman disease (MCD) involves multiple enlarged lymph nodes and can cause severe symptoms and multi-organ system impairment due to systemic inflammation. MCD can be caused by infection with Human Herpes Virus-8 (“HHV-8-associated MCD”) or can occur for unknown reasons (HHV-8-negative or idiopathic “iMCD”).
It is extremely important to differentiate this disease into either UCD, HHV-8-associated MCD, or iMCD because they can have different symptoms, treatments, and prognoses.
What are the symptoms of Castleman disease?
The symptoms of Castleman disease vary between subtypes. Even within these subtypes, the presentation can be very heterogeneous – meaning that different patients will display different symptoms. The heterogeneity of presentation, combined with the fact that these symptoms can appear in other diseases, makes diagnosis by symptoms extremely difficult. This is a reason why the biopsy requirement for diagnosis is so important.
UCD Symptoms: Patients often show no symptoms except for the discomfort associated with the enlarged lymph node as well as symptoms that may be related to the enlarged lymph node pushing on nearby structures. Patients can occasionally present with systemic MCD-like symptoms. Other UCD patients can go on to develop paraneoplastic pemphigus, which is a very serious disorder requiring prompt treatment.
MCD Symptoms: Patients can present with a wide range of symptoms from mild flu-like episodes to severe, life-threatening multi-organ failure. Some of the systemic symptoms include: Fever and night sweats, Fatigue, Loss of appetite, Cachexia (weakness and wasting of the body, muscle atrophy, unintended weight loss), Nausea and vomiting, Numbness in the hands and feet, Enlarged liver and/or spleen, Eruption of cherry hemangiomas (cherry red papules that form from an abnormal growth of blood vessels on the skin), Edema (swelling), Ascites (fluid accumulation in the abdomen), and/or other symptoms of fluid overload (extensive fluid accumulation, if present, may result in a net weight gain despite cachexia), Decreased urine output and systemic toxicity due to kidney failure, Bruising, Easy bleeding, and Risk of infection due to bone marrow failure.
What causes Castleman disease? Who is at risk?
The HHV-8 positive MCD subtype is known to be associated with HHV-8 virus infection simultaneously with some form of immunosuppression (such as HIV or genetic causes). Immunosuppression is in fact the most significant risk factor for HHV-8 associated iMCD.
However, it is not understood why only a few patients with HHV-8+ infection and immunosuppression develop Castleman disease. Although the HHV-8 virus is contagious, the vast majority of HHV-8+ patients will not develop Castleman disease.
All cases of UCD and idiopathic MCD have an unknown cause. There are no known risk factors; there is no evidence of any food, lifestyle, or environmental exposure associated with these diseases. There is no known account of a patient contracting Castleman disease directly from another individual.
Are there any clinical trials for Castleman disease?
Yes. There are currently two open clinical trials for patients with Castleman disease, one in the USA and one in China.
In the USA, a clinical trial is open for patients with idiopathic (HHV-8-negative) multicentric Castleman disease (iMCD) at the University of Pennsylvania and University of Arkansas for Medical Sciences. The clinical trial is for the medication sirolimus. Patients with iMCD who still have significant symptoms after trying either siltuximab or tocilizumab are eligible to enroll in the trial. Patients can learn more about the trial at: cdcn.org/trial
In China, the Peking Union Medical College Hospital in Beijing is currently recruiting for a clinical trial that is studying the medications bortezomib, cyclophosphamide and dexamethasone (BCD regimen) for Castleman disease. The trial is open for patients who are newly diagnosed idiopathic multicentric Castleman disease. More information about this trial can be found here.
Is Castleman disease a form of cancer or does it cause cancer?
As of 2019, CD is not considered a form of cancer. More research is needed as our understanding of CD is still limited. Patients with iMCD and HHV-8 MCD have symptoms and laboratory abnormalities similar to some aggressive lymphomas. These symptoms and lab abnormalities can also be similar to some autoimmune disorders. Therefore, the classification of CD remains difficult.
There is an increased risk of hematologic malignancies in iMCD. The exact reason is unknown. Further research is needed to better understand the size and the cause of the risk increase.
Is it safe for me to get pregnant?
No one has ever studied or reported any data on this important question, so unfortunately, we can’t provide a definitive answer to this question. Addressing this important question has been difficult due to how rare CD is.
What is the CDCN doing to combat Castleman disease?
A major reason that patients are dying from CD is that it is so poorly understood by the medical community. We’re here to change that. The CDCN was developed in August 2012 by a group of physicians and researchers dedicated to finding a cure for Castleman disease and supporting patients along the way. So far we have:
- Connected the global community of 800+ physicians and researchers through the three largest-ever Castleman disease research meetings and an online discussion board
- Assembled a Scientific Advisory Board of 30 experts from eight countries
- Established the current state of medical knowledge for Castleman disease
- Engaged patients on the Scientific Advisory Board, Leadership Team, and all research meetings, as well as through the annual Patient Summit, physician referrals, and educational materials
How can I help accelerate finding a cure for Castleman disease?
- Share your Castleman disease data: Be sure that you have taken 15-20 minutes to enroll in the ACCELERATE Castleman disease patient research study, which is collecting data on patients from around the world to identify patterns and information to improve treatment and care. This is a huge opportunity to do your part to help solve the mysteries of CD.
- Share samples: Be sure that you have taken 5 minutes to express interest in contributing samples for ongoing and future research studies, click here.
- Donate funds for CD research: Research is not possible without funding. You can donate or share the link with friends and family to enable life-saving CD research.
- Join the Warriors: Patients can join the Castleman Warrior team and create their own Warrior fundraising pages to share with family and friends.
- Connect: Make sure you have joined the CDCN Patient/Loved One Community, click here to join and gain access to all available information, resources, and peer support groups.
- Let us know how we can help! Email info@castlemannetwork.org or call (610)304-0696 if you would like more information or have any questions.
Does Dr. David Fajgenbaum treat patients at the University of Pennsylvania?
Dr. Fajgenbaum is currently a full time researcher and he does not treat patients. However, if you are interested in being treated at the University of Pennsylvania, Dr. Sunita Nasta and Dr. Adam Cohen are part of the CSTL and are the physicians that provide care for Castleman disease patients. In addition, the CDCN keeps a referral list of physicians around the world that we know to have significant experience treating Castleman disease patients. The list is available to all patients who register with the CDCN.