Idiopathic multicentric Castleman disease (often called iMCD) is a rare disorder that involves an overactive immune system, leading to inflammation throughout the body. The disease affects multiple lymph nodes, causing them to enlarge and produce excessive amounts of inflammatory chemicals called cytokines. This results in symptoms such as fever, fatigue, and problems in several organs. The term “idiopathic” means the cause is unknown. Diagnosing iMCD requires excluding other conditions, such as infections or cancers, that could cause similar symptoms.
Patients with iMCD commonly experience:
Enlarged lymph nodes in multiple areas (often the neck, chest, armpits, and abdomen).
Fever and persistent tiredness.
Weight loss and loss of appetite.
Swelling caused by fluid retention (oedema), which can be generalized (anasarca) or localized.
Anaemia (low red blood cells), leading to fatigue and shortness of breath.
Problems with kidney function.
Laboratory abnormalities, such as elevated inflammatory markers (e.g., C-reactive protein) and low albumin levels in the blood.
Symptoms that flare up and improve over time (remitting and relapsing pattern).
iMCD has two main subtypes:
iMCD-TAFRO: More aggressive and involves severe fluid buildup, low platelet counts (thrombocytopenia), kidney dysfunction, and widespread inflammation.
iMCD-NOS (Not Otherwise Specified): Usually has fewer fluid issues, but often shows increased protein (gamma globulin) levels in the blood and a higher platelet count.
The exact cause of iMCD is unknown. Researchers suspect it results from abnormal activity of the immune system that leads to high levels of inflammation-causing proteins (cytokines), especially interleukin-6 (IL-6). Some studies suggest that genetics, a still-unidentified virus, or an inflammatory trigger might contribute to the disease, but no single clear cause has been identified.
Castleman disease is classified as either “unicentric” or “multicentric”:
Unicentric Castleman disease (UCD) affects a single lymph node or a single group of lymph nodes in one part of the body. It typically presents with fewer symptoms and can often be successfully treated by surgically removing the affected node.
Multicentric Castleman disease (MCD), including iMCD, affects multiple lymph nodes and may involve other organs, causing widespread symptoms and inflammation throughout the body. It typically requires treatments that target the immune system, rather than surgery alone.
No, iMCD is not considered cancer. Instead, it is a serious immune system disorder involving excessive immune activity and widespread inflammation. However, patients with iMCD may have a higher risk of developing certain cancers over time, including lymphomas (cancers involving the lymph nodes).
The diagnosis of iMCD is usually made through examination of a lymph node biopsy by a pathologist. Under the microscope, the pathologist looks for specific features, such as reduced or “atrophic” germinal centres (areas where immune cells normally grow), and an increased number of plasma cells. Because these findings are also seen in other diseases like HIV, HHV8 infection, and certain cancers, these conditions must be ruled out before confirming a diagnosis of iMCD.
Immunohistochemistry is a special test used to detect specific proteins in tissue samples. In iMCD, IHC helps rule out other disorders by confirming the absence of the HHV8 virus (a common cause of another form of Castleman disease). The test also shows that plasma cells (immune cells involved in antibody production) are polyclonal (varied), helping differentiate iMCD from certain types of lymphoma or cancer.
Your doctor may also request blood tests to look for high levels of inflammatory markers, cytokines such as IL-6, and abnormal protein levels in the blood, which support the diagnosis and help monitor disease activity.
The prognosis of iMCD can vary widely. Some patients respond well to treatment and can control symptoms effectively, while others may experience severe flare-ups and significant organ dysfunction.
The subtype of the disease plays a major role in prognosis:
Patients with iMCD-TAFRO typically have more severe symptoms, multiple organ problems, and a more aggressive course, with shorter survival if not treated effectively.
Patients with iMCD-NOS usually have a less aggressive course, but may still experience relapses and symptoms that require ongoing treatment.
Effective treatments often include medications targeting cytokines, particularly IL-6 (such as siltuximab or tocilizumab). Steroids, chemotherapy, and other immunomodulating therapies may also be used. Close medical follow-up is crucial for managing symptoms, preventing complications, and monitoring for the development of any associated cancers.
How was my diagnosis of iMCD confirmed?
Which subtype of iMCD do I have, and what does that mean for my treatment?
What additional tests will I need to monitor my condition?
What treatments are recommended for me, and what side effects can I expect?
How frequently should I see a specialist to manage my disease?
How will we monitor for disease flare-ups or relapses?
Am I at higher risk of developing lymphoma or other cancers?
Are there lifestyle changes or precautions that can help me manage my symptoms?
What resources or support groups are available for people with Castleman disease?