Castleman disease describes a group of rare disorders with a wide range of symptoms. People with these conditions have enlarged lymph nodes that have a similar appearance when reviewed under the microscope. Castleman disease is first classified based on the number of regions of enlarged lymph nodes that have these abnormal features. [rx]Unicentric Castleman disease (UCD) involves a single enlarged lymph node or single region of enlarged lymph nodes whereas multicentric Castleman disease (MCD) involves multiple regions of enlarged lymph nodes. There are two subtypes of MCD. One subtype is caused by human herpesvirus-8 (HHV-8; also known as Kaposi sarcoma–associated herpesvirus). These cases are called HHV-8-associated MCD. The other subtype includes MCD patients who are negative for the HHV-8 virus, and the cause is unknown. These cases are called HHV-8 negative or “idiopathic” MCD (iMCD).[rx]

Castleman disease is a rare and complex condition that affects the lymph nodes in your body. In this article, we’ll break down the types, causes, symptoms, diagnostic tests, treatments, and drugs associated with Castleman disease in simple and easy-to-understand language.

Types of Castleman Disease:

1. Unicentric Castleman Disease (UCD): This is the more common type, where only one lymph node or a group of nearby lymph nodes are affected. It’s usually not as severe as the multicentric form.
2. Multicentric Castleman Disease (MCD): In this type, multiple lymph nodes throughout your body are affected. MCD is more severe and can have more serious symptoms.

Causes of Castleman Disease:

The exact cause of UCD and iMCD is not known. 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 report of a patient developing UCD or iMCD from contact with another individual with UCD or iMCD. Viruses, genetic mutations acquired over the course of life and inflammation have all been proposed as possible causes of UCD. Recent research suggests that acquired genetic mutations are the likely cause of UCD.[rx]

HHV-8 is the well-established cause of HHV-8-associated MCD, which accounts for approximately 25-50% of all cases of MCD. HHV-8-associated MCD often occurs in individuals infected with human immunodeficiency virus (HIV). The HIV weakens the ability of the immune system to control the HHV-8 infection. The HHV-8 virus causes MCD by making its own IL-6 and causing cells to rapidly multiply.[rx]

Approximately 50-75% of MCD cases are negative for HHV-8 and the cause is unknown or “idiopathic.” Recently, four possible causes have been hypothesized: a virus, genetic mutation acquired over the course of life, an inherited genetic mutation or autoimmunity. Some researchers speculate that increased production of interleukin-6 (IL-6) due to one of the above causes may be involved in the development of iMCD. IL-6 is a substance normally produced by cells within the lymph nodes (plasma cells) and in healthy individuals coordinates the immune response to infection. However, IL-6 is not elevated in all patients, and neutralizing IL-6 is not effective for the treatment of all patients.[rx]

Castleman disease isn’t caused by infections or lifestyle factors like smoking or diet. Instead, it’s thought to result from an overactive immune system, although the exact cause is still not fully understood.[rx]

Symptoms of Castleman Disease:

Unicentric Castleman Disease (UCD)

UCD is characterized by a single enlarged lymph node or multiple enlarged lymph nodes in a single region of the body, such as the chest, abdomen or neck. Most patients with UCD have no symptoms (asymptomatic). UCD symptoms tend to be mild and occur secondary to compression of surrounding structures by rapidly enlarging lymph nodes. Occasionally, patients experience symptoms due to the size and location of the growth. [rx]For example, a growth may form next to a vein, resulting in a bulge and possible obstruction in the involved blood vessel. Less commonly, some UCD patients experience systemic inflammatory symptoms such as fever, fatigue, excessive sweating, weight loss and skin rash as well as laboratory abnormalities such as low hemoglobin and elevated C-reactive protein. These symptoms are typically seen in MCD. These symptoms usually disappear after surgical excision of the UCD lymph node.[rx]

Multicentric Castleman Disease (MCD)

Patients with multicentric Castleman disease (MCD) have enlarged lymph nodes in multiple regions and more severe symptoms than UCD. Some patients are HHV-8 positive (HHV-8 MCD) whereas other patients are HHV-8-negative/idiopathic (iMCD).

Signs and symptoms of iMCD include:

• Flu-like symptoms: fever, fatigue, weight loss, night sweats, loss of appetite, nausea and vomiting
• Abnormally large lymph nodes, typically in the neck, armpit, collarbone and groin
• Enlarged spleen or liver
• Eruptive cherry hemangiomas
• Edema (swelling), ascites (fluid accumulation in the abdomen) and/or other symptoms of fluid accumulation
• Peripheral neuropathy (numbness in the hands and feet)
• Elevated inflammatory markers (C-reactive protein, erythrocyte sedimentation rate)
• Kidney dysfunction
• Low albumin
• Anemia (low amount of red blood cells)[rx]
• Low or high platelet counts
• Elevated immunoglobulins or gamma globulins

1. Enlarged Lymph Nodes: The most common symptom is the enlargement of lymph nodes in various parts of your body.
2. Fever: Many people with Castleman disease experience recurrent fevers.
3. Fatigue: You might feel extremely tired and lacking in energy.
4. Night Sweats: Excessive sweating during the night is a common symptom.
5. Weakness: You may feel physically weak and unable to perform daily tasks.
6. Loss of Appetite: Castleman disease can lead to a decreased desire to eat.
7. Unexplained Weight Loss: You might lose weight without trying.
8. Swollen Spleen or Liver: In some cases, these organs can become enlarged.
9. Nausea and Vomiting: You may experience these digestive symptoms.
10. Numbness or Tingling: Rarely, Castleman disease can affect nerves, causing these sensations.
11. Skin Rash: Some people develop skin rashes.
12. Difficulty Breathing: Severe cases can lead to breathing problems due to enlarged lymph nodes pressing on the airways.
13. Swollen Face and Neck: Enlarged lymph nodes in these areas can cause visible swelling.
14. Joint Pain: You might experience pain in your joints.
15. Mouth Sores: These can develop in some cases.
16. Edema (Swelling): Swelling in the legs, ankles, or other body parts can occur.
17. Anemia: A decrease in red blood cells may lead to anemia.
18. Increased Susceptibility to Infections: Your immune system may become weakened.
19. Neuropathy: Rarely, Castleman disease can affect nerves, causing symptoms like numbness and weakness.
20. Enlarged Tonsils and Adenoids: These are the tissues at the back of your throat, and they can become enlarged in some cases.

Diagnostic Tests for Castleman Disease:

1. Biopsy: A small piece of tissue from an enlarged lymph node is removed and examined under a microscope.
2. Blood Tests: These can help identify abnormalities in your blood cells and immune system.
3. Imaging Scans: CT scans, MRI scans, or PET scans can visualize the lymph nodes and other affected areas.
4. Lymph Node Aspiration: A needle is used to remove fluid from a lymph node for analysis.
5. Bone Marrow Biopsy: In some cases, a sample of bone marrow is taken to check for abnormalities.
6. Lymphangiography: Dye is injected into the lymphatic system to help visualize lymph nodes.
7. Genetic Testing: Rarely, genetic testing can be done to look for specific genetic mutations associated with Castleman disease.

Treatments for Castleman Disease:

1. Surgery: In unicentric Castleman disease, surgical removal of the affected lymph node is often curative.
2. Radiation Therapy: High-energy rays are used to target and shrink enlarged lymph nodes.
3. Corticosteroids: These anti-inflammatory drugs can help manage symptoms and reduce inflammation.
4. Interleukin-6 (IL-6) Inhibitors: Medications like tocilizumab can be used to block IL-6, a protein involved in the disease.
5. Chemotherapy: Powerful drugs are used to kill rapidly dividing cells, including abnormal ones.
6. Antiviral Medications: If a viral infection is contributing to the disease, antiviral drugs may be prescribed.
7. Immunotherapy: This treatment aims to boost your immune system to fight the disease.
8. Plasmapheresis: In severe cases, this procedure removes harmful antibodies from your blood.
9. Stem Cell Transplant: For some MCD patients, a stem cell transplant may be necessary to replace damaged cells.
10. Clinical Trials: New treatments and medications are constantly being researched in clinical trials, and you may have the opportunity to participate.
11. Supportive Care: Managing symptoms and complications, such as pain relief and infection control, is an essential part of treatment.

Drugs for Castleman Disease:

1. Tocilizumab (Actemra): This IL-6 inhibitor can reduce inflammation and manage symptoms.
2. Corticosteroids: Medications like prednisone can help control inflammation.
3. Chemotherapy Drugs: Various chemotherapy drugs, such as rituximab and cyclophosphamide, may be used.
4. Antiviral Medications: If a viral infection is suspected, antiviral drugs like ganciclovir may be prescribed.
5. Immunosuppressants: Drugs like cyclosporine can help suppress the immune system’s response.
6. Pomalidomide (Pomalyst): This medication can be used in some cases of MCD.
7. Sirolimus (Rapamune): It’s an immunosuppressive drug that may be considered.
8. Valganciclovir (Valcyte): Used to treat viral infections, particularly in MCD.
9. Methotrexate: Sometimes used to manage symptoms.
10. Rituximab (Rituxan): A monoclonal antibody that targets specific cells involved in the disease.
11. Eltrombopag (Promacta): It can help increase platelet counts in some cases.
12. Antibiotics: These may be prescribed if there’s a bacterial infection associated with the disease.
13. Supportive Medications: Medications to manage symptoms like pain, nausea, and fever.
14. IV Immunoglobulin (IVIG): Used to boost the immune system.
15. Filgrastim (Neupogen): Stimulates the production of white blood cells.
16. Cidofovir (Vistide): An antiviral medication sometimes used.
17. Adalimumab (Humira): Used in some cases to manage symptoms.
18. Thalidomide (Thalomid): Considered in certain situations.
19. Cyclosporine: An immunosuppressant drug that may be used.
20. Imiquimod (Aldara): Applied topically to treat skin symptoms.

Surgery is considered to be the first-line treatment option for all cases of UCD. Surgical removal of the affected lymph node(s) usually results in cure. However, recurrences of UCD have been reported. Sometimes, removing the enlarged lymph node(s) is not possible. If surgical excision is not possible, treatment is recommended for symptomatic patients. If symptoms are due to compression, rituximab is recommended. If symptoms are due to an inflammatory syndrome, anti-interleukin-6 (IL-6) therapy is recommended. If these treatments are not effective, radiation may be needed.[rx]

Idiopathic Multicentric Castleman Disease (iMCD)

First-line treatment for iMCD is anti-IL-6 therapy with siltuximab (or tocilizumab if siltuximab is not available). Siltuximab is the only FDA-approved treatment for iMCD, and patients who respond to siltuximab tend to have long-term responses. For critically ill patients, chemotherapy and corticosteroids are recommended if the patient’s disease is progressing while on siltuxumab. Approximately half of iMCD patients do not improve with anti-IL-6 therapy, and for these patients, other treatments such as rituximab and sirolimus can be used.[rx]

HHV-8-Associated Multicentric Castleman Disease (HHV-8 Positive MCD)

Rituximab is often used to eliminate a type of immune cell called the B lymphocyte. It is highly effective for HHV-8-associated MCD, but occasionally antivirals and/or cytotoxic chemotherapies are also needed.[rx]

Castleman disease is a complex condition, and the treatment approach depends on the type and severity of the disease. It’s essential to work closely with your healthcare team to develop a personalized treatment plan that addresses your specific needs. Remember that medical advancements are ongoing, and new treatments may become available in the future to improve the management of Castleman disease.[rx]

 

Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, previous medical  history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. Thank you for giving your valuable time to read the article.

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