Understanding Castleman Disease: Subtypes, Symptoms, and Modern Treatments

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• What is Castleman Disease?
• Localized vs. Multicentric Castleman Disease
• Symptoms and Diagnosis
• Interleukin-6 Role in Castleman Disease
• Castleman Disease Treatment Options
• Prognosis and Outcomes
• Full Transcript

What is Castleman Disease?

Castleman disease is a rare lymphoproliferative disorder that affects the lymph nodes. Dr. Nikhil Munshi, MD, emphasizes that while it is not cancer, it can be a debilitating condition for patients. The disease involves abnormal growth of lymph nodes and can cause significant systemic symptoms. According to Dr. Munshi, Castleman disease is infrequently diagnosed due to its rarity. Patients often experience a range of symptoms that can severely impact their quality of life.

Localized vs. Multicentric Castleman Disease

Castleman disease presents in two distinct forms with different treatment approaches. Localized Castleman disease involves enlargement of lymph nodes in a single area, such as the neck, chest, or abdomen. Dr. Nikhil Munshi, MD, explains that surgical removal of the affected lymph nodes is often curative for this subtype. Multicentric Castleman disease involves multiple lymph node regions throughout the body. This form is more symptomatic and cannot be treated with surgery alone. Pathologically, multicentric Castleman disease often presents as the plasmacytic variant, while localized disease is more commonly the hyaline-vascular type.

Symptoms and Diagnosis

Multicentric Castleman disease causes significant systemic symptoms that can be debilitating. Patients may experience severe fatigue, fever, night sweats, and weight loss. Dr. Nikhil Munshi, MD, notes that laboratory findings include elevated platelet count, anemia, low albumin levels, and increased immunoglobulins. These symptoms can be so severe that patients may become bedridden. Diagnosis involves imaging to identify lymph node enlargement and laboratory tests to assess inflammatory markers. The C-reactive protein (CRP) test serves as a valuable surrogate marker for disease activity.

Interleukin-6 Role in Castleman Disease

Interleukin-6 (IL-6) plays a central role in driving Castleman disease symptoms and pathology. Dr. Nikhil Munshi, MD, explains that this cytokine is significantly elevated in patients with multicentric Castleman disease. High IL-6 levels directly contribute to the inflammatory symptoms and laboratory abnormalities seen in the condition. Measurement of IL-6 levels or its surrogate marker, C-reactive protein, helps in diagnosis and monitoring treatment response. This understanding of IL-6's role has led to the development of targeted therapies that specifically block this cytokine pathway.

Castleman Disease Treatment Options

Modern treatment approaches for Castleman disease target the underlying cytokine dysfunction. Siltuximab, an anti-IL-6 monoclonal antibody, is approved for treatment and shows significant efficacy. Dr. Nikhil Munshi, MD, describes how siltuximab improves symptoms and controls lymph node enlargement. Tocilizumab, which targets the IL-6 receptor, is approved in Japan for Castleman disease treatment. Before these targeted therapies, rituximab (an anti-CD20 antibody) was used and provided benefit by targeting B cells. Treatment selection depends on the disease subtype and individual patient factors.

Prognosis and Outcomes

Castleman disease can be effectively managed with appropriate treatment strategies. Dr. Nikhil Munshi, MD, emphasizes that localized Castleman disease often has a curative outcome with surgical intervention. For multicentric Castleman disease, targeted therapies like siltuximab provide long-term disease control. Patients can achieve significant symptom improvement and maintain quality of life with proper treatment. While not curable in the multicentric form, the disease can be controlled successfully for extended periods. Dr. Anton Titov, MD, discusses these positive outcomes with Dr. Munshi, highlighting the importance of accurate diagnosis and appropriate treatment selection.

Full Transcript

Dr. Anton Titov, MD: Professor Munshi, you wrote a very interesting review about Castleman disease. What is Castleman disease and what is the treatment of Castleman disease? It's a fascinating and very difficult condition.

Dr. Nikhil Munshi, MD: Yeah, so that is a very difficult condition. It is very infrequently diagnosed because it's not a very common condition. The good news about Castleman disease in general is that I tell patients it's not cancer. So the same rules may or may not apply.

However, it can be debilitating. Patients have a lot of symptoms. It is what we call a lymphoproliferative disorder where lymph nodes are the problem. Without being too detailed, because it's so uncommon, it's a condition where there are two types.

What is called localized Castleman disease is where only lymph nodes on one side are enlarged. It could be the neck, it could be the chest, it could be the abdomen—only one side. The second type of Castleman disease is called multicentric, where multiple lymph nodes are involved.

For the first type, the localized type, doing surgery is the way to go. Because you can remove the local lymph nodes and nothing is left. It's almost curative. On the other side, the multicentric Castleman disease is in multiple places. We cannot do surgery at multiple places. They are more symptomatic.

In pathology, they are also quite often what is called a plasmacytic type Castleman disease, instead of the other one, which is called hyaline-vascular type. This multicentric type comes with lots of symptomatology. Most of these symptoms are driven by a cytokine called interleukin six.

We measure IL-6 level, which is high. A surrogate for IL-6 is a test called CRP, C-reactive protein, which is high. There are various other laboratory changes. We observe higher platelet count, patients having anemia, having low albumin, having nonspecific immunoglobulin increase, etc.

These are the patients who have significant symptoms. They could be bedridden sometimes because of those and they need treatment. Fortunately, we have a drug that is approved for Castleman disease. Its name is called siltuximab and it is an anti-IL-6 antibody.

There is significant efficacy both to improve the symptoms and also to control the lymph node enlargement, etc. There is another drug not approved in the United States but in Japan it is approved, called tocilizumab, which also targets IL-6 but through its receptor.

Then there are other drugs like rituximab, which is targeting B cells and used for lymphoma, that have been utilized before the era of tocilizumab and siltuximab. Rituximab has provided benefit as well. So we have to keep those in mind as we treat this patient population.

Dr. Nikhil Munshi, MD: But Castleman disease can be effectively treated and can be controlled quite successfully for a long-term period. Also, in many cases, a curative outcome in localized Castleman disease is possible.