Castleman Disease: Symptoms, Diagnosis & Multicentric Treatment Options

Introduction

Multicentric Castleman disease (MCD) is a rare but serious condition that affects the lymph nodes and related tissues. First identified by Dr. Benjamin Castleman in the 1950s, this disease can present with a wide range of symptoms, from mild to life-threatening. Unlike unicentric Castleman disease, which is confined to a single region, MCD involves multiple areas of the body and can lead to systemic inflammation and organ dysfunction. This article aims to provide a clear, patient-friendly overview of MCD, including its risk factors, symptoms, diagnostic tests, treatment options, and home care strategies. Understanding these aspects can empower patients to take an active role in managing their condition alongside healthcare providers.

What is Multicentric Castleman Disease?

Multicentric Castleman disease (MCD) is a rare disorder that affects multiple lymph node regions and can cause systemic symptoms. This article will explore the risk factors, symptoms, diagnostic tests, medications, procedures, and home care strategies that can help manage the condition.

Description of Multicentric Castleman Disease

Multicentric Castleman disease (MCD) is a rare lymphoproliferative disorder, meaning it causes abnormal overgrowth of cells in the lymphatic system. The lymphatic system is a crucial part of the immune system, helping the body fight infections and maintain fluid balance. In MCD, multiple lymph nodes become enlarged, and the disease can affect organs such as the liver, spleen, and bone marrow. Unlike unicentric Castleman disease, which is localized to one area, MCD involves multiple regions, leading to more widespread symptoms.

The progression of MCD can vary significantly from patient to patient. Some individuals may experience mild symptoms, while others may develop severe complications, including organ failure. MCD is often associated with systemic inflammation, which can cause fever, weight loss, and fatigue. In some cases, MCD is linked to infections like human herpesvirus 8 (HHV-8) or conditions such as HIV.

Though rare, MCD can be life-threatening if not properly managed. Recent studies estimate that there are approximately 1,200 to 1,500 new cases of MCD each year in the United States. Early diagnosis and treatment are crucial for improving outcomes and managing symptoms effectively.

Risk Factors for Developing Multicentric Castleman Disease

Lifestyle Risk Factors

While no specific lifestyle factors directly cause MCD, certain behaviors may increase the risk of developing infections that can trigger the disease. For example, individuals engaging in high-risk behaviors, such as unprotected sex or intravenous drug use, are more likely to contract HIV, a known risk factor for MCD. Additionally, exposure to environments where human herpesvirus 8 (HHV-8) is prevalent, such as certain regions of Africa, may increase the likelihood of developing MCD. Although lifestyle changes alone cannot prevent MCD, reducing exposure to these infections can lower the risk.

Medical Risk Factors

Several medical conditions are associated with an increased risk of developing MCD. One of the most significant is infection with HHV-8, a virus commonly found in individuals with compromised immune systems, such as those living with HIV. HHV-8-associated MCD is more common in people with HIV, particularly those not receiving effective antiretroviral therapy (ART). Additionally, individuals with autoimmune diseases or other conditions that weaken the immune system may be at higher risk for MCD.

Genetic and Age-Related Risk Factors

Although MCD is not typically considered a genetic disease, some genetic predispositions may increase the likelihood of developing the condition. For example, individuals with a family history of immune system disorders may be more susceptible to MCD. Age is another important factor; MCD is more commonly diagnosed in adults between the ages of 40 and 60, though it can affect individuals outside this range, including children and older adults.

In summary, while the exact cause of MCD is not fully understood, a combination of lifestyle, medical, and genetic factors can contribute to its development. Understanding these risk factors can help patients and healthcare providers identify the condition early and take steps to manage it effectively.

Symptoms of Multicentric Castleman Disease

Fever

Fever is a common symptom of multicentric Castleman disease (MCD), affecting approximately 80% of patients. It results from the body’s immune response to the overproduction of inflammatory proteins, such as interleukin-6 (IL-6). This immune response raises body temperature as it attempts to fight off perceived abnormalities. Fevers in MCD can be persistent or intermittent, with some patients experiencing low-grade fevers and others facing higher, more debilitating temperatures.

Fatigue

Fatigue affects about 70-80% of MCD patients. This overwhelming tiredness is often due to the body’s chronic inflammatory state, which consumes energy and resources. Fatigue can also be worsened by anemia, another common MCD symptom. The immune system’s overproduction of cytokines like IL-6 contributes to this exhaustion. Fatigue in MCD is typically severe and does not improve with rest, significantly impacting daily activities and quality of life.

Weight Loss

Unexplained weight loss occurs in approximately 60% of MCD patients. This symptom is often linked to the body’s inflammatory response, which increases metabolism and reduces appetite. The overproduction of IL-6 and other cytokines can lead to a catabolic state, where the body breaks down muscle and fat for energy. Weight loss in MCD can be gradual or rapid, depending on disease severity. Monitoring weight changes is crucial, as significant weight loss can lead to malnutrition and further complications.

Night Sweats

Night sweats are reported in about 50-60% of MCD patients. These episodes of excessive sweating during sleep are often caused by the body’s inflammatory response, particularly the release of cytokines like IL-6. Night sweats can be drenching and may disrupt sleep, leading to further fatigue. They are more common during active phases of the disease and can signal flare-ups. Patients should report night sweats to their healthcare provider, as they may indicate disease progression.

Lymphadenopathy

Lymphadenopathy, or swollen lymph nodes, is a hallmark of MCD, occurring in nearly 100% of patients. The lymph nodes become enlarged due to abnormal immune cell growth, a direct result of the disease. Lymphadenopathy can occur in multiple regions, including the neck, armpits, and groin. Swollen lymph nodes may be painless or tender. In some cases, they can grow large enough to cause discomfort or pressure on surrounding tissues and organs.

Anemia

Anemia affects about 60-70% of MCD patients. It occurs when the body lacks enough healthy red blood cells to carry oxygen to tissues. In MCD, chronic inflammation often interferes with red blood cell production. Additionally, the overproduction of IL-6 can suppress the bone marrow, further reducing red blood cell production. Symptoms of anemia include fatigue, weakness, and shortness of breath.

Thrombocytopenia

Thrombocytopenia, or low platelet count, affects approximately 30-40% of MCD patients. Platelets are essential for blood clotting, and a low count can lead to easy bruising, prolonged bleeding, and increased risk of complications. In MCD, thrombocytopenia is often due to bone marrow suppression caused by cytokine overproduction. It may also be linked to splenomegaly, where the spleen sequesters platelets, reducing their availability in the bloodstream.

Hypergammaglobulinemia

Hypergammaglobulinemia, or elevated antibody levels, is seen in about 50-60% of MCD patients. This occurs because the immune system is hyperactive, producing excessive immunoglobulins (antibodies). While antibodies typically fight infections, in MCD, this overproduction is part of the abnormal immune response. Hypergammaglobulinemia can increase infection risk, as the immune system becomes dysregulated and less effective at targeting specific pathogens.

Hepatomegaly

Hepatomegaly, or an enlarged liver, occurs in about 30-40% of MCD patients. The liver may enlarge due to the accumulation of inflammatory cells and proteins, as well as the overproduction of antibodies. Hepatomegaly can cause discomfort or pain in the upper right abdomen and may be associated with liver dysfunction. In severe cases, liver function tests may show abnormalities, indicating impaired liver function.

Splenomegaly

Splenomegaly, or an enlarged spleen, is present in approximately 40-50% of MCD patients. The spleen plays a key role in filtering blood and managing the immune response. In MCD, the spleen may enlarge due to the overproduction of immune cells and cytokines. Splenomegaly can cause discomfort or pain in the left upper abdomen and may lead to complications such as thrombocytopenia, as the spleen sequesters platelets. In some cases, an enlarged spleen may need to be surgically removed if it causes significant symptoms or complications.

Treatment Options for Multicentric Castleman Disease

Medications for Castleman Disease

Siltuximab

Siltuximab is a monoclonal antibody that targets interleukin-6 (IL-6), a protein involved in inflammation and abnormal cell growth in multicentric Castleman disease (MCD). By blocking IL-6, siltuximab helps reduce inflammation and slow the progression of the disease.

It is typically the first-line treatment for MCD patients who are not infected with HIV or HHV-8. Administered via intravenous (IV) infusion every three weeks, siltuximab is recommended when the disease is active and causing significant symptoms.

Many patients experience relief from symptoms such as fatigue, fever, and enlarged lymph nodes within weeks to months. Long-term stabilization of the disease is also possible.

Rituximab

Rituximab is a monoclonal antibody that targets CD20, a protein found on certain immune cells. It helps control the overactive immune response seen in MCD by depleting these cells.

Rituximab is often used in MCD patients who are infected with HIV or HHV-8, or when siltuximab is ineffective. It is administered through IV infusion over several weeks.

Rituximab can reduce the size of lymph nodes and improve symptoms such as fever and night sweats. Response times vary, and additional treatment courses may be needed depending on disease activity.

Corticosteroids

Corticosteroids are anti-inflammatory medications that suppress the immune system to reduce inflammation. They are often used to quickly control symptoms, especially during flare-ups.

These drugs are typically used short-term or in combination with other therapies, such as rituximab or chemotherapy. Corticosteroids can be taken orally or administered via IV, depending on the severity of the disease.

Symptom relief is usually rapid, occurring within days. However, long-term use is avoided due to potential side effects, including weight gain, high blood pressure, and an increased risk of infection.

Chemotherapy

Chemotherapy uses drugs to kill rapidly dividing cells, including abnormal immune cells in MCD. It is generally reserved for severe cases or when other treatments, such as siltuximab or rituximab, are ineffective.

Chemotherapy may also be combined with other therapies for better disease control. While it can reduce lymph node size and improve symptoms, side effects such as fatigue, nausea, and an increased risk of infection are common. Multiple treatment cycles may be required.

Tocilizumab

Tocilizumab is a monoclonal antibody that blocks the IL-6 receptor, reducing inflammation and slowing disease progression in MCD.

It is often used in patients who do not respond to siltuximab or when IL-6 levels remain elevated despite other treatments. Tocilizumab is administered via IV infusion or subcutaneous injection every two to four weeks.

Patients may experience symptom improvement within weeks to months, but regular monitoring is necessary to assess the effectiveness of the treatment.

Interferon-alpha

Interferon-alpha is a protein that regulates the immune system and has antiviral and anti-tumor properties. It is sometimes used in MCD to control the overactive immune response.

Typically used in patients who do not respond to other treatments or in more aggressive cases, interferon-alpha is administered through injections several times a week.

While it can reduce symptoms and slow disease progression, side effects such as flu-like symptoms, fatigue, and depression are common. Long-term therapy may be required for some patients.

Anakinra

Anakinra blocks interleukin-1 (IL-1), another protein involved in inflammation. It is used in MCD to reduce inflammation and control symptoms.

Typically used in patients who do not respond to IL-6-targeted therapies like siltuximab or tocilizumab, anakinra is administered through daily subcutaneous injections.

Symptom relief may occur within weeks, but the effectiveness of the treatment can vary. Regular monitoring is essential to evaluate the response to therapy.

Thalidomide

Thalidomide is an immunomodulatory drug that regulates the immune system and reduces inflammation. It is sometimes used in MCD to control symptoms and slow disease progression.

Thalidomide is typically used in patients who do not respond to other treatments or in more aggressive cases. It is taken orally, usually once a day.

While it can improve symptoms, side effects such as drowsiness, constipation, and nerve damage are possible. Long-term therapy may be needed for some patients.

Pomalidomide

Pomalidomide is a newer immunomodulatory drug similar to thalidomide but with fewer side effects. It helps regulate the immune system and reduce inflammation in MCD.

Pomalidomide is typically used in patients who do not respond to other treatments or in more aggressive cases. It is taken orally, usually once a day.

Symptom improvement may occur within weeks to months, but regular monitoring is required to assess the effectiveness of the treatment.

Lenalidomide

Lenalidomide is another immunomodulatory drug that helps regulate the immune system and reduce inflammation. It is used in MCD to control symptoms and slow disease progression.

Lenalidomide is typically used in patients who do not respond to other treatments or in more aggressive cases. It is taken orally, usually once a day.

Patients may experience symptom improvement within weeks to months, but regular monitoring is necessary to evaluate the treatment’s effectiveness.

Improving Multicentric Castleman Disease and Seeking Medical Help

While there is no cure for multicentric Castleman disease (MCD), several strategies can help manage symptoms and improve quality of life. In addition to medical treatments, patients can adopt certain lifestyle changes:

1. Rest and Sleep: Fatigue is a common symptom of Castleman disease. Ensuring adequate rest and sleep can help manage energy levels and reduce fatigue.
2. Healthy Diet: A balanced diet rich in fruits, vegetables, and lean proteins supports the immune system and overall health.
3. Hydration: Staying well-hydrated is important, especially if experiencing fever or night sweats.
4. Stress Management: Stress can worsen symptoms. Relaxation techniques such as meditation, deep breathing, or yoga can be beneficial.
5. Exercise: Gentle exercise, such as walking or stretching, can improve circulation and reduce fatigue. However, it’s important to avoid overexertion.

Telemedicine offers a convenient way to manage MCD, allowing patients to consult healthcare providers from home. This is especially helpful for those with mobility issues or living in remote areas. If symptoms worsen or new complications arise, seeking prompt medical help is crucial. Telemedicine provides timely access to care, helping manage the condition effectively.

Living with Multicentric Castleman Disease: Tips for Better Quality of Life

Living with MCD can be challenging, but there are steps you can take to improve your quality of life:

1. Stay Informed: Understanding your condition and treatment options empowers you to make informed decisions about your care.
2. Build a Support Network: Connecting with family, friends, or support groups provides emotional support and practical assistance.
3. Follow Your Treatment Plan: Adhering to prescribed treatments and attending regular follow-up appointments is crucial for managing MCD.
4. Monitor Symptoms: Track any changes in symptoms and report them to your healthcare provider. Early intervention can prevent complications.
5. Focus on Self-Care: Prioritize activities that promote relaxation and well-being, such as hobbies, reading, or spending time with loved ones.

Conclusion

Multicentric Castleman disease (MCD) is a rare and complex condition that requires careful management. Early diagnosis and treatment are essential for controlling symptoms and preventing complications. With the right combination of medical treatments and lifestyle adjustments, many patients can achieve a better quality of life.

If you or a loved one are experiencing symptoms of MCD, it’s important to seek medical help as soon as possible. Our primary care telemedicine practice is here to provide you with convenient, compassionate care from the comfort of your home. Reach out to us today to schedule a consultation and take the first step toward managing your health.

James Kingsley

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