Castleman Disease: Types, Symptoms & Treatment Options

What is Castleman Disease?

Castleman disease is a rare lymphoproliferative disorder that affects the lymphatic system, which is responsible for filtering lymph fluid and supporting immune function. It causes an abnormal overgrowth of cells within the lymph nodes—the small, bean-shaped structures that filter harmful substances and support immune function. This uncontrolled growth can interfere with the body’s ability to regulate immunity and fight infections effectively.

Although not classified as a cancer, Castleman disease shares features with both lymphomas and autoimmune inflammatory disorders. It can develop in any part of the body, but most commonly affects the chest, abdomen, neck, and underarm regions. Castleman disease is classified based on the number of lymph node regions involved: Unicentric Castleman Disease (UCD) affects a single lymph node region, while Multicentric Castleman Disease (MCD) involves multiple lymph node areas and systemic inflammation.

Why Does Castleman Disease Occur?

The exact cause of Castleman disease remains unclear, but it is believed to arise from an abnormal immune response that triggers excessive growth of lymph node cells. This overactivity disrupts normal immune regulation, leading to inflammation and tissue enlargement.

According to the National Institutes of Health (NIH), human herpesvirus-8 (HHV-8) infection is a key contributor in many cases of HHV-8–associated Multicentric Castleman Disease (MCD), particularly in people living with HIV/AIDS—particularly among individuals with weakened immune systems, such as those living with HIV/AIDS. The virus promotes the release of inflammatory proteins that drive uncontrolled lymph node growth.

In idiopathic Multicentric Castleman Disease (iMCD), which is not linked to HHV-8 infection, overproduction of interleukin-6 (IL-6) is a central pathogenic mechanism, a signalling molecule responsible for inflammation and immune activation. Elevated IL-6 levels stimulate abnormal cell proliferation and cause many of the systemic symptoms seen in Castleman disease, including fever, fatigue, and swollen lymph nodes.

What Are the Different Types of Castleman Disease?

Castleman disease is broadly categorised based on the number and distribution of lymph nodes involved.

The two main Castleman disease types are:

• Unicentric Castleman Disease (UCD):
  Involves a single lymph node or region and is typically benign and localised. It is the most common subtype and often asymptomatic. It is the more common and typically localised type. Most people with UCD do not experience widespread symptoms, and the condition is often curable through surgical removal of the affected node.
• Multicentric Castleman Disease (MCD):
  nvolves multiple lymph node regions and systemic inflammation. Subtypes include HHV-8–associated MCD, idiopathic MCD (iMCD), and POEMS-associated MCD and causes systemic inflammation. MCD is more aggressive and may lead to symptoms such as fever, fatigue, and organ enlargement. It is frequently associated with human herpesvirus-8 (HHV-8) infection or an overactive immune system, particularly in individuals with compromised immunity.

How Do the Symptoms of Castleman Disease Differ by Type?

The Castleman disease symptoms vary depending on whether it affects a single lymph node region (unicentric) or multiple regions (multicentric).

a. Unicentric Castleman Disease (UCD) Symptoms:

UCD is often silent and discovered incidentally during imaging or surgery for another condition. When symptoms appear, they are usually due to the enlarged lymph node pressing on nearby structures.

• Painless swollen lymph nodes
• A feeling of fullness or pressure in the chest or abdomen
• Fatigue or mild fever (less common)

b. Multicentric Castleman Disease (MCD) Symptoms:

MCD produces more widespread and systemic effects because it involves several lymph node regions and triggers inflammation throughout the body.

• Persistent fever and night sweats
• Unexplained weight loss and loss of appetite
• Severe fatigue and weakness
• Enlarged liver or spleen (hepatosplenomegaly)
• Fluid accumulation in the abdomen (ascites), chest (pleural effusion), or pericardium (pericardial effusion)
• Anaemia, frequent infections, and nerve damage in advanced cases

What Increases the Risk of Castleman Disease?

While anyone can develop Castleman disease, certain factors increase the likelihood of occurrence—especially for the multicentric form.

These include:

• Infection with HHV-8 or HIV: The presence of human herpesvirus-8 (HHV-8), particularly in individuals with HIV/AIDS, significantly raises the risk by triggering immune overactivation.
• Weakened immune system: People with suppressed or compromised immunity are more vulnerable to abnormal lymph node growth and viral reactivation.
• Male gender: Men, especially middle-aged or older, are more commonly affected by Multicentric Castleman Disease (MCD).
• Age: Castleman disease can occur at any age but is most commonly diagnosed in adults between 40 and 60 years.
• Chronic inflammatory or autoimmune conditions: Persistent inflammation or immune dysregulation may predispose individuals to the abnormal immune responses seen in Castleman disease.

How Is Castleman Disease Diagnosed?

Diagnosing Castleman disease involves a thorough clinical evaluation supported by laboratory and imaging studies. Because its symptoms often resemble those of infections or lymphomas, a combination of tests is used to confirm the condition and determine its type.

1. Physical Examination:
   The doctor checks for enlarged lymph nodes, particularly in the neck, underarms, chest, or abdomen, and looks for signs of organ enlargement, such as the liver or spleen.
2. Blood and Urine Tests:
   These help evaluate immune system activity, detect anaemia or infection, and measure inflammatory markers like C-reactive protein (CRP) and interleukin-6 (IL-6).
3. Imaging Tests:
   CT scans, MRI, or PET scans are used to locate enlarged lymph nodes and assess whether the disease is localised (unicentric) or widespread (multicentric).
4. Lymph Node Biopsy:
   This is the gold standard for diagnosis, revealing characteristic histopathological patterns such as hyaline-vascular, plasma cell, or mixed variants. A small tissue sample from an affected lymph node is examined under a microscope to identify the abnormal cell growth patterns characteristic of Castleman disease.

Diagnostic Tests for Castleman Disease

Accurate diagnosis of Castleman disease requires a combination of blood, imaging, and tissue-based investigations to identify the underlying cause and extent of lymph node involvement.

The following diagnostic evaluations may be recommended:

• Complete Blood Count (CBC):
  Helps detect anaemia, infection, or abnormal white blood cell counts, often associated with immune dysregulation.
• C-Reactive Protein (CRP) and Erythrocyte Sedimentation Rate (ESR): Non-specific markers of inflammation that are frequently elevated in MCD.
• Interleukin-6 (IL-6) Levels:
  High IL-6 levels are a hallmark of Castleman disease and correlate with disease severity and systemic inflammation.
• HIV and HHV-8 Testing:
  Identifies viral infections that can trigger or worsen Multicentric Castleman Disease, especially in immunocompromised individuals.
• Imaging Scans (CT, MRI, or PET-CT):

Identify the extent and metabolic activity of lymphadenopathy and help distinguish UCD from MCD.

• Lymph Node Biopsy:
  The gold standard for confirmation. Histopathological examination reveals characteristic lymphoid cell overgrowth and structural changes consistent with Castleman disease.

What Are the Treatment Options for Castleman Disease?

The Castleman disease treatment varies depending on whether it is unicentric (UCD) or multicentric (MCD). The primary goals are to control abnormal lymph node growth, reduce inflammation, and manage associated infections or immune dysfunction.

How Is Unicentric Castleman Disease (UCD) Treated?

Treatment for Unicentric Castleman Disease focuses on eliminating the single affected lymph node and relieving pressure on surrounding organs. Most patients achieve complete recovery after treatment.

• Surgical Removal:
  The first-line and most effective treatment. Removing the affected lymph node is usually curative, with minimal chance of recurrence.
• Radiation Therapy:
  Recommended when surgical removal is not possible due to the node’s location or surgical risk. It helps shrink or control lymph node growth.
• Medication:
  Corticosteroids may be prescribed before or after surgery to reduce inflammation and lymph node swelling.

How Is Multicentric Castleman Disease (MCD) Treated?

Since Multicentric Castleman Disease affects multiple lymph nodes and involves systemic inflammation, treatment focuses on immune modulation, infection control, and symptom relief.

• Monoclonal Antibody Therapy:

Siltuximab (anti–IL-6) and Tocilizumab (anti–IL-6 receptor) are standard treatments for idiopathic MCD (iMCD), shown to induce durable remission in many patients.

• Antiviral Therapy:
  Used when HHV-8 or HIV infection is detected, to suppress viral activity and improve immune function.
• Corticosteroids:
  Help control immune system overactivity and provide quick relief from systemic symptoms like fever and fatigue.
• Chemotherapy or Immunotherapy:
  Chemotherapy or immunomodulatory therapy (e.g., rituximab for HHV-8–positive MCD) may be used when IL-6–targeted therapy is ineffective or contraindicated.
• Stem Cell Transplant:
  Autologous or allogeneic stem cell transplantation may be considered in select patients with refractory iMCD or relapse after multiple therapies

What Complications Can Castleman Disease Cause?

If left untreated or poorly managed, Castleman Disease—particularly the multicentric form—can lead to several serious complications due to chronic inflammation and immune system dysregulation.

These include:

• Disease recurrence:

More common in MCD, especially in patients with persistent viral infection or suboptimal response to therapy.

• Increased risk of lymphoma:
  Chronic immune activation and abnormal cell growth can predispose patients to non-Hodgkin or Hodgkin lymphoma over time.
• Organ failure:
  Long-term inflammation may lead to liver, kidney, or bone marrow failure, affecting the body’s ability to filter toxins, produce blood cells, or maintain fluid balance.
• Severe infections:
  An overactive yet weakened immune system makes patients more susceptible to bacterial, viral, or fungal infections.
• Peripheral neuropathy or amyloidosis (rare complications):
  Result from chronic inflammation or associated syndromes such as POEMS.

What Is the Outlook for Someone with Castleman Disease?

Prognosis depends on disease subtype, viral status (HHV-8 positive or idiopathic), and response to therapy. UCD generally has an excellent prognosis, while outcomes in MCD vary. For Unicentric Castleman Disease (UCD), the outlook is highly favourable. Most patients experience a complete recovery following surgical removal of the affected lymph node, with little risk of recurrence or long-term complications.

In contrast, the outlook for Multicentric Castleman Disease (MCD) varies based on factors such as the presence of HHV-8 or HIV infection, the severity of immune dysfunction, and the response to treatment. Thanks to medical advances—particularly IL-6–targeted therapies like siltuximab and tocilizumab—many patients now achieve long-term remission, improved survival rates, and a better quality of life.

Regular follow-up and monitoring remain essential to detect relapses early and manage associated health risks effectively.

How Can Patients Manage Castleman Disease in Daily Life?

Living with Castleman disease requires consistent medical follow-up and lifestyle adjustments to maintain immune health and prevent complications. The following steps can help patients manage their condition effectively:

• Follow regular medical check-ups:
  Routine monitoring helps track lymph node size, organ function, and treatment response, ensuring timely intervention if symptoms recur.
• Manage infections promptly:
  Even minor infections can worsen inflammation or trigger flare-ups. Early medical attention and adherence to prescribed medications are crucial.
• Maintain a balanced diet and stay hydrated:
  A nutrient-rich diet supports the immune system and aids recovery. Adequate hydration helps regulate body functions and reduce fatigue.
• Get sufficient rest and manage stress:
  Proper sleep and stress management techniques, such as meditation or light exercise, help strengthen immunity and improve overall well-being.
• Seek emotional and psychological support:
  Coping with a chronic illness can be challenging. Support groups or counselling can help manage anxiety and improve mental health.
• Report new or worsening symptoms immediately:
  Promptly informing your doctor about any unusual symptoms ensures early detection of relapse or secondary infections.

Conclusion

Castleman disease is a rare disorder of nodes that highlights the importance of early detection and precise diagnosis. Recognising Castleman disease symptoms early, confirming the condition through reliable testing, and beginning the right Castleman disease treatment can greatly improve patient outcomes. With advancements in targeted immunotherapy and IL-6 pathway inhibitors, long-term remission and survival have improved significantly in both HHV-8–associated and idiopathic MCD, many individuals today can manage the disease effectively and enjoy a good quality of life.

At Metropolis Healthcare, patients have access to over 4,000 specialised tests, including advanced immunological and viral studies, supported by expert analysis and quick turnaround times. With 10,000+ home sample collection touchpoints, full body health check-ups, and booking convenience via website, app, WhatsApp, or phone, Metropolis ensures high-quality, accessible, and accurate diagnostics. Trusted for its excellence in speciality testing, Metropolis Healthcare continues to empower better health outcomes with precision, reliability, and care.

FAQs

Is Castleman Disease a Cancer?

No, Castleman disease is not cancer, though it can mimic lymphoma due to lymph node enlargement. However, patients with MCC have a higher risk of developing lymphoma later.

Can Castleman Disease Be Cured?

Unicentric Castleman Disease can be cured with surgery. Castleman disease, though chronic, can be managed effectively with targeted and antiviral therapies.

Who Is Most at Risk of Castleman Disease?

People aged 40–60, particularly men with weakened immunity or HIV infection, are at higher risk.

What Is the Difference Between Unicentric and Multicentric Castleman Disease?

• Unicentric: Affects one lymph node regionlocaliseded and curable by surgery.
• Multicentric: Involves multiple nodes; systemic with flu-like symptoms and needs lifelong management.

Is Castleman Disease Hereditary?

No, there is no evidence suggesting that Castleman Disease is inherited or passed genetically within families.

References

https://pmc.ncbi.nlm.nih.gov/articles/PMC8663817/

https://www.mayoclinic.org/diseases-conditions/castleman-disease/symptoms-causes/syc-20543017

https://my.clevelandclinic.org/health/diseases/17920-castleman-disease

https://www.pathologyoutlines.com/topic/lymphnodescastleman.html