Castleman-Kojima Disease: Symptoms, Causes, and Treatment Guide

Introduction to Castleman-Kojima Disease

Castleman-Kojima disease is a rare and complex condition that affects the lymphatic system, a crucial component of the immune system. First identified in the 1950s by Dr. Benjamin Castleman and later further characterized by Dr. Masahiro Kojima, this disease is distinguished by abnormal growth of lymph nodes and related tissues. While it is not classified as cancer, its symptoms and progression often mimic lymphoma, underscoring the importance of early diagnosis and treatment. Due to its rarity and variability, understanding and managing Castleman-Kojima disease can be challenging, leaving many patients with unanswered questions about their condition.

This article is designed to provide clear, patient-centered information about Castleman-Kojima disease. We will explore its risk factors, symptoms, diagnostic methods, treatment options, and lifestyle adjustments that may help manage symptoms. By the end, you will have a clearer understanding of this condition and how to work with your healthcare provider to achieve the best possible care.

What is Castleman-Kojima Disease?

Castleman-Kojima disease is a rare disorder characterized by the abnormal growth of lymphatic tissue. This article will examine its risk factors, symptoms, diagnostic techniques, treatment strategies, and approaches to managing the condition at home.

Understanding Castleman-Kojima Disease

Also referred to as Castleman disease, Castleman-Kojima disease is a rare condition that impacts the lymphatic system, which plays a vital role in filtering harmful substances and supporting immune function. The disease manifests in two primary forms:

1. Unicentric Castleman disease (UCD): This form involves a single lymph node or region and is typically localized.
2. Multicentric Castleman disease (MCD): This form affects multiple lymph nodes and can cause systemic symptoms.

The progression of Castleman-Kojima disease depends on its subtype. UCD may not produce significant symptoms, while MCD can lead to widespread inflammation and complications, including organ dysfunction. In some cases, MCD is associated with conditions such as HIV or human herpesvirus-8 (HHV-8), which can influence the severity of the disease and its treatment approach.

Castleman-Kojima disease is extremely rare, with an estimated 6,500 to 7,700 new cases diagnosed annually in the United States. It can affect individuals of all ages, although certain subtypes are more common in specific populations. Early recognition and diagnosis are critical for effective management and the prevention of complications.

Risk Factors for Castleman-Kojima Disease

Lifestyle Risk Factors

Although Castleman-Kojima disease is not directly caused by lifestyle choices, certain factors may influence its development or progression. For example, individuals with weakened immune systems—such as those undergoing chemotherapy or living with chronic illnesses—may have a higher risk of developing the multicentric form of the disease. Additionally, exposure to infections like human herpesvirus-8 (HHV-8) has been linked to the disease, particularly in individuals with compromised immunity.

Adopting a healthy lifestyle, including a balanced diet, regular physical activity, and effective stress management, can support overall immune health. While these measures cannot prevent Castleman-Kojima disease, they may help reduce the risk of complications and improve overall well-being.

Medical Risk Factors

Certain medical conditions that suppress the immune system, such as HIV/AIDS, are significant risk factors for Castleman-Kojima disease, particularly the multicentric subtype. Individuals with autoimmune disorders or those receiving immunosuppressive therapy may also face an increased risk. Additionally, specific viral infections, including HHV-8, are strongly associated with the development of multicentric Castleman disease.

People with a history of other lymphatic or hematologic disorders should remain vigilant for symptoms of Castleman-Kojima disease, as these conditions may overlap or coexist. Regular follow-ups with a healthcare provider are essential for early detection and effective management.

Genetic and Age-Related Risk Factors

Although Castleman-Kojima disease is not typically hereditary, some genetic predispositions may contribute to its development. Ongoing research is focused on identifying specific genetic markers or mutations associated with the disease. Age is another factor, as the unicentric form is more commonly diagnosed in younger adults, while the multicentric form tends to affect older individuals, particularly those over 50.

Understanding your family medical history and discussing any concerns with your healthcare provider can help identify potential risks and guide appropriate screening and monitoring strategies.

Symptoms of Castleman-Kojima Disease

Fever

Fever occurs in 40–60% of patients with Castleman-Kojima disease and is often one of the earliest symptoms. It may be intermittent or persistent and is caused by the overproduction of inflammatory cytokines, such as interleukin-6 (IL-6), a hallmark of the disease. These cytokines activate the immune response, leading to an elevated body temperature. Patients may experience fever episodes that are unrelated to infections or other common causes, prompting further investigation by their healthcare provider.

Fatigue

Fatigue affects 70–80% of patients and can significantly impact quality of life. This symptom is driven by chronic inflammation, which diverts the body’s energy to address what it perceives as an ongoing threat. Additionally, anemia—a common complication of Castleman-Kojima disease—can exacerbate fatigue by reducing the oxygen supply to tissues. Patients often describe this fatigue as persistent and unrelenting, even after rest, making it difficult to carry out daily activities.

Weight Loss

Unintentional weight loss is reported in 50–60% of cases. This occurs because the inflammatory response in Castleman-Kojima disease increases metabolism while suppressing appetite. Cytokines like IL-6 can impair the body’s ability to process nutrients effectively, leading to muscle wasting and fat loss. Patients may notice a gradual or sudden decrease in weight without changes to their diet or exercise habits.

Lymphadenopathy

Enlarged lymph nodes, or lymphadenopathy, are present in nearly all patients with Castleman-Kojima disease. This symptom results from the overgrowth of lymphatic tissue due to excessive immune activation. The lymph nodes may be painless or tender and are commonly found in the neck, armpits, or groin. In some cases, the lymph nodes may grow large enough to compress nearby structures, causing additional symptoms such as difficulty breathing or swallowing.

Night Sweats

Night sweats affect 40–50% of patients and are often described as episodes so intense that they require a change of clothes or bedding. These episodes result from the body’s inflammatory response, which disrupts normal temperature regulation. When combined with fever, weight loss, and lymphadenopathy, night sweats may signal an underlying systemic condition like Castleman-Kojima disease.

Anemia

Anemia is present in 60–70% of patients and is characterized by a reduced number of red blood cells or lower hemoglobin levels. Chronic inflammation suppresses red blood cell production in the bone marrow, while excessive cytokine production interferes with iron metabolism, further contributing to anemia. Symptoms of anemia include fatigue, pale skin, shortness of breath, and dizziness, which may overlap with other manifestations of the disease.

Thrombocytopenia

Thrombocytopenia, or a low platelet count, affects 30–40% of patients. Platelets are essential for blood clotting, and their reduction can lead to easy bruising, prolonged bleeding, or petechiae (small red or purple spots on the skin). In Castleman-Kojima disease, thrombocytopenia may result from bone marrow suppression or increased platelet destruction due to immune system dysregulation.

Hypergammaglobulinemia

Hypergammaglobulinemia, an elevated level of antibodies in the blood, occurs in 50–60% of cases. This condition results from overactivation of B cells, a type of immune cell. While excessive antibody production may seem beneficial, it can disrupt immune balance and contribute to inflammation. Patients may not experience direct symptoms, but hypergammaglobulinemia is often detected through blood tests during diagnosis.

Hepatomegaly

Hepatomegaly, or an enlarged liver, is found in 20–30% of patients. This occurs due to the accumulation of inflammatory cells and abnormal immune activity in the liver. Patients may experience discomfort or a sensation of fullness in the upper right abdomen. Abnormal liver function tests may also prompt further investigation.

Splenomegaly

Splenomegaly, or an enlarged spleen, affects 30–40% of patients. The spleen plays a key role in filtering blood and regulating immune responses. In Castleman-Kojima disease, excessive immune activation can cause spleen enlargement, leading to symptoms such as abdominal pain, a feeling of fullness, or reduced infection-fighting ability. Splenomegaly is often detected through imaging studies or physical examinations.

Health Conditions with Similar Symptoms to Castleman-Kojima Disease

Hodgkin Lymphoma

Hodgkin lymphoma is a type of cancer that originates in the lymphatic system, a critical component of the immune system. It develops when abnormal white blood cells, known as Reed-Sternberg cells, multiply uncontrollably within the lymph nodes. Common symptoms include swollen lymph nodes, persistent fatigue, fever, and night sweats. Early diagnosis often makes Hodgkin lymphoma highly treatable.

How to Differentiate Hodgkin Lymphoma from Castleman-Kojima Disease

Both Hodgkin lymphoma and Castleman-Kojima disease can present with swollen lymph nodes, fever, night sweats, and fatigue. However, persistent itching and unexplained weight loss are more characteristic of Hodgkin lymphoma. A definitive diagnosis requires a lymph node biopsy, which identifies Reed-Sternberg cells in Hodgkin lymphoma—cells that are absent in Castleman-Kojima disease. Imaging studies, such as PET or CT scans, may reveal distinct lymph node patterns, while elevated lactate dehydrogenase (LDH) levels in blood tests are more commonly associated with Hodgkin lymphoma.

Non-Hodgkin Lymphoma

Non-Hodgkin lymphoma encompasses a diverse group of cancers originating in the lymphatic system, each with unique features and behaviors. Symptoms often include swollen lymph nodes, fever, night sweats, and fatigue, though the severity and presentation can vary depending on the specific subtype.

How to Differentiate Non-Hodgkin Lymphoma from Castleman-Kojima Disease

Non-Hodgkin lymphoma and Castleman-Kojima disease share overlapping symptoms, such as swollen lymph nodes, fever, and fatigue. However, non-Hodgkin lymphoma is more likely to cause abdominal pain, chest pain, or breathing difficulties due to lymph node involvement in these areas. A lymph node biopsy is essential for diagnosis, as malignant lymphocytes are present in non-Hodgkin lymphoma, whereas Castleman-Kojima disease shows non-cancerous changes like vascular proliferation. Molecular testing may also detect genetic markers specific to non-Hodgkin lymphoma.

Sarcoidosis

Sarcoidosis is an inflammatory condition characterized by granulomas—small clusters of immune cells—that can form in various organs, most commonly the lungs and lymph nodes. Symptoms include fatigue, fever, swollen lymph nodes, and shortness of breath. While the exact cause is unknown, it is believed to involve an overactive immune response.

How to Differentiate Sarcoidosis from Castleman-Kojima Disease

Both sarcoidosis and Castleman-Kojima disease can cause swollen lymph nodes, fatigue, and fever. However, sarcoidosis frequently affects the lungs, leading to respiratory symptoms such as coughing and shortness of breath, which are uncommon in Castleman-Kojima disease. A biopsy in sarcoidosis reveals granulomas, which are absent in Castleman-Kojima disease. Imaging studies, such as chest X-rays or CT scans, often show lung involvement in sarcoidosis, while Castleman-Kojima disease primarily affects lymph nodes. Elevated calcium levels or increased angiotensin-converting enzyme (ACE) levels in blood tests are also more indicative of sarcoidosis.

Systemic Lupus Erythematosus (SLE)

Systemic lupus erythematosus (SLE) is a chronic autoimmune condition that can affect multiple organs, including the skin, joints, kidneys, and heart. Symptoms vary widely but often include fatigue, joint pain, skin rashes, fever, and swollen lymph nodes. SLE occurs when the immune system mistakenly attacks healthy tissues.

How to Differentiate SLE from Castleman-Kojima Disease

Both SLE and Castleman-Kojima disease can cause fatigue, fever, and swollen lymph nodes. However, SLE is more likely to present with joint pain, a butterfly-shaped rash across the cheeks and nose, and kidney complications, none of which are typical of Castleman-Kojima disease. Blood tests in SLE often detect antinuclear antibodies (ANA) and other autoantibodies, such as anti-dsDNA or anti-Smith antibodies, which are absent in Castleman-Kojima disease. Additionally, low levels of complement proteins (C3 and C4) are common in SLE but not in Castleman-Kojima disease.

Multiple Myeloma

Multiple myeloma is a cancer of plasma cells, a type of white blood cell found in the bone marrow. It results in the overproduction of abnormal plasma cells, which can interfere with the production of healthy blood cells. Symptoms include bone pain, fatigue, frequent infections, elevated calcium levels, and kidney damage.

How to Differentiate Multiple Myeloma from Castleman-Kojima Disease

Both multiple myeloma and Castleman-Kojima disease can cause fatigue and recurrent infections. However, multiple myeloma is more likely to present with bone pain, fractures, and high calcium levels, which are not typical of Castleman-Kojima disease. Blood tests in multiple myeloma often reveal elevated monoclonal protein (M-protein) levels and signs of kidney dysfunction. A bone marrow biopsy is crucial for diagnosing multiple myeloma, as it shows an overgrowth of abnormal plasma cells, which are absent in Castleman-Kojima disease. Imaging studies, such as X-rays or MRIs, may also reveal bone lesions in multiple myeloma, which are not seen in Castleman-Kojima disease.

Infectious Mononucleosis

Infectious mononucleosis, commonly referred to as “mono,” is a viral illness caused by the Epstein-Barr virus (EBV). It is most common in teenagers and young adults. Symptoms include fatigue, fever, swollen lymph nodes, a sore throat, and an enlarged spleen. Mono is typically self-limiting and resolves within a few weeks.

How to Differentiate Mono from Castleman-Kojima Disease

Both mono and Castleman-Kojima disease can cause swollen lymph nodes, fever, and fatigue. However, mono is more likely to present with a sore throat and an enlarged spleen, which are not features of Castleman-Kojima disease. Blood tests in mono often show an increase in atypical lymphocytes, and specific tests for EBV antibodies can confirm the diagnosis. These findings are absent in Castleman-Kojima disease, which typically requires a lymph node biopsy for diagnosis.

Autoimmune Lymphoproliferative Syndrome (ALPS)

Autoimmune lymphoproliferative syndrome (ALPS) is a rare genetic disorder that affects the immune system. It leads to an overproduction of lymphocytes, resulting in swollen lymph nodes, an enlarged spleen, and autoimmune complications such as anemia or low platelet counts. ALPS is usually diagnosed in childhood.

How to Differentiate ALPS from Castleman-Kojima Disease

Both ALPS and Castleman-Kojima disease can cause swollen lymph nodes and fatigue. However, ALPS is more likely to present with autoimmune symptoms, such as anemia, low platelet counts, or autoimmune skin conditions, which are not typical of Castleman-Kojima disease. Blood tests in ALPS often reveal elevated double-negative T-cells, which are absent in Castleman-Kojima disease. Genetic testing can confirm mutations in the FAS gene associated with ALPS.

Tuberculosis (TB)

Tuberculosis (TB) is a bacterial infection caused by Mycobacterium tuberculosis. While it primarily affects the lungs, it can also involve other parts of the body, such as the lymph nodes, bones, or kidneys. Symptoms include fever, night sweats, weight loss, fatigue, and a persistent cough.

How to Differentiate TB from Castleman-Kojima Disease

Both TB and Castleman-Kojima disease can cause fever, night sweats, and swollen lymph nodes. However, TB is more likely to present with a persistent cough, weight loss, and lung-related symptoms. Diagnostic tests for TB include a skin test (PPD), blood tests like the interferon-gamma release assay, and imaging studies such as chest X-rays, which may reveal lung abnormalities. A biopsy in TB typically shows granulomas with caseating necrosis, which are absent in Castleman-Kojima disease.

Chronic Lymphocytic Leukemia (CLL)

Chronic lymphocytic leukemia (CLL) is a slow-progressing cancer of the blood and bone marrow. It leads to the overproduction of abnormal lymphocytes, causing symptoms such as fatigue, swollen lymph nodes, and frequent infections. CLL is more common in older adults.

How to Differentiate CLL from Castleman-Kojima Disease

Both CLL and Castleman-Kojima disease can cause swollen lymph nodes and fatigue. However, CLL is more likely to show an increased number of abnormal lymphocytes in the blood, which can be detected through a complete blood count (CBC) and flow cytometry. These findings are not typical of Castleman-Kojima disease. Genetic testing in CLL may reveal specific mutations, such as deletions in chromosome 13q, which are not associated with Castleman-Kojima disease.

Castleman Disease

Castleman disease is a rare condition that affects the lymph nodes and immune system tissues. It has two main forms: unicentric (affecting a single lymph node) and multicentric (affecting multiple lymph nodes). Symptoms include swollen lymph nodes, fever, fatigue, and night sweats. Although not a cancer, Castleman disease can mimic cancer in its presentation.

How to Differentiate Castleman Disease from Castleman-Kojima Disease

Castleman-Kojima disease is a subtype of Castleman disease, distinguished by specific histological features and systemic symptoms. A lymph node biopsy is often necessary to identify the unique histological patterns of Castleman-Kojima disease, such as increased vascularity and cellular changes. Blood tests, imaging studies, and clinical symptoms can further aid in distinguishing between these subtypes. Consulting a specialist with expertise in Castleman disease is essential for an accurate diagnosis.

Treatment Options for Castleman-Kojima Disease

Medications for Castleman-Kojima Disease

Siltuximab

Siltuximab is a monoclonal antibody that targets interleukin-6 (IL-6), a protein involved in inflammation and immune system regulation. By inhibiting IL-6, this medication helps control the overactive immune response characteristic of Castleman-Kojima disease.

It is considered a first-line treatment for multicentric Castleman disease (MCD) in patients who are not infected with HIV or human herpesvirus-8 (HHV-8). Siltuximab is administered intravenously, typically every three weeks.

Many patients experience significant symptom relief, such as reduced lymph node size and improved energy levels, within weeks of starting treatment.

Rituximab

Rituximab is a monoclonal antibody that targets CD20, a protein found on certain immune cells. By depleting these overactive cells, rituximab helps manage Castleman-Kojima disease.

This medication is often used for HHV-8-associated MCD or in patients who do not respond to IL-6 inhibitors like siltuximab. Rituximab is administered intravenously in cycles over several weeks.

Patients may notice a reduction in lymph node size and an improvement in systemic symptoms within weeks, although full benefits may take longer to appear.

Tocilizumab

Tocilizumab, another IL-6 inhibitor, works by blocking the IL-6 receptor to reduce inflammation. It is frequently used when patients cannot tolerate siltuximab or when siltuximab is unavailable.

Administered via intravenous infusion or subcutaneous injection every two to four weeks, tocilizumab can alleviate systemic symptoms such as fatigue and fever within weeks of starting therapy.

Corticosteroids

Corticosteroids, including prednisone and dexamethasone, are powerful anti-inflammatory medications that suppress the immune system. They are often used short-term to quickly reduce inflammation and control acute symptoms, particularly in severe cases or in combination with other therapies.

While corticosteroids provide rapid relief, long-term use is generally avoided due to potential side effects such as weight gain, high blood sugar, and weakened bones.

Chemotherapy

Chemotherapy involves the use of drugs like cyclophosphamide and etoposide to destroy rapidly dividing cells, including those contributing to Castleman-Kojima disease. This approach is typically reserved for severe or treatment-resistant cases of MCD.

Administered in cycles either orally or intravenously, chemotherapy can reduce lymph node size and systemic symptoms. However, side effects such as fatigue, nausea, and hair loss are common and may require supportive care.

Interferon-Alpha

Interferon-alpha is a protein with immune-modulating and antiviral properties that can help reduce inflammation and control disease activity. It is often used when other therapies are ineffective or as part of a combination treatment plan.

Administered via injection several times a week, interferon-alpha may gradually improve symptoms. However, it can cause flu-like side effects, including fatigue and fever.

Anakinra

Anakinra, an IL-1 receptor antagonist, works by blocking interleukin-1 to reduce immune system overactivity. It is used off-label for Castleman-Kojima disease, particularly in patients who do not respond to IL-6 inhibitors.

Administered as a daily subcutaneous injection, anakinra can improve symptoms within weeks. However, the need for daily injections may be inconvenient for some patients.

Thalidomide

Thalidomide is an immunomodulatory drug that reduces inflammation and inhibits abnormal blood vessel growth. It is typically used for refractory cases or as part of combination therapy.

Taken orally once daily, thalidomide can improve symptoms but carries risks such as nerve damage and blood clots, necessitating close monitoring by a healthcare provider.

Lenalidomide

Lenalidomide, a derivative of thalidomide, offers similar immunomodulatory effects with a potentially lower risk of side effects. It helps regulate the immune system and reduce inflammation.

Often prescribed for patients who cannot tolerate thalidomide or as part of combination therapy, lenalidomide is taken orally once daily. Symptom relief may occur within weeks, but regular monitoring is essential to manage potential side effects, such as low blood counts.

Pomalidomide

Pomalidomide, a more potent derivative of thalidomide, modulates the immune system and reduces inflammation. It is typically reserved for advanced or treatment-resistant cases of Castleman-Kojima disease.

Administered orally once daily, pomalidomide can improve symptoms within weeks. However, side effects such as fatigue and low blood counts may require dose adjustments and careful monitoring.

Procedures for Castleman-Kojima Disease

Currently, there are no widely used procedural interventions for Castleman-Kojima disease. Treatment primarily focuses on medical management with medications tailored to the patient’s specific needs.

Improving Castleman-Kojima Disease and Seeking Medical Help

In addition to medical treatments, certain lifestyle changes can help alleviate symptoms and enhance overall well-being:

1. Balanced Diet: Consuming a nutrient-rich diet supports immune health and promotes overall wellness.
2. Regular Exercise: Gentle activities such as walking or yoga can help boost energy levels and reduce fatigue.
3. Stress Management: Techniques like meditation or deep breathing exercises can help manage stress, which may exacerbate symptoms.
4. Adequate Sleep: Prioritizing restful sleep enhances the body’s ability to recover and manage symptoms effectively.

If symptoms worsen or new complications arise, it is important to seek medical attention promptly. Telemedicine offers a convenient way to consult healthcare professionals from the comfort of your home, ensuring timely care and support.

Living with Castleman-Kojima Disease: Tips for Better Quality of Life

Managing Castleman-Kojima disease can be challenging, but the following steps can help improve your quality of life:

1. Build a Support Network: Connect with family, friends, or support groups to share experiences and receive emotional support.
2. Follow Your Treatment Plan: Adhering to prescribed medications and attending follow-up appointments is essential for managing symptoms and preventing complications.
3. Stay Informed: Educate yourself about the condition to better understand treatment options and advocate for your care.
4. Communicate with Your Healthcare Team: Maintain open and honest communication with your doctors to address concerns or changes in your condition promptly.

Conclusion

Castleman-Kojima disease is a rare and complex condition that requires careful management and a personalized treatment approach. Early diagnosis and timely intervention are crucial for improving outcomes and enhancing quality of life.

If you or a loved one are experiencing symptoms or have been diagnosed with Castleman-Kojima disease, our telemedicine practice is here to help. Schedule a virtual consultation with our experienced primary care providers to receive personalized care and guidance from the comfort of your home.

By staying proactive and working closely with your healthcare team, you can effectively manage this condition and lead a fulfilling life.

James Kingsley

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