Castleman Disease: Understanding a Rare and Mysterious Immune Disorder

By SWA

Castleman disease (CD) is a rare and complex disorder that affects the lymphatic system, often confusing both patients and medical professionals due to its overlapping features with cancer and autoimmune diseases. Each year, approximately 5,000 people in the United States are diagnosed with this condition. Despite being noncancerous, Castleman disease can behave aggressively, leading to serious complications if left untreated.

What is Castleman Disease?

Castleman disease refers to a group of disorders involving an overgrowth of cells in the body’s lymph nodes. Though benign (noncancerous), these growths can activate the immune system excessively, causing a cascade of inflammatory proteins that may damage vital organs such as the liver, kidneys, and bone marrow.

There are two primary types of Castleman disease:

  • Unicentric Castleman Disease (UCD): Affects a single group of lymph nodes, typically in the chest or abdomen. This is the more common and localized form of the disease.
  • Multicentric Castleman Disease (MCD): Affects multiple lymph node regions and can have more widespread, systemic symptoms. MCD is further classified into subtypes, including idiopathic MCD (iMCD) and HHV-8-associated MCD, depending on its cause.

Is Castleman Disease Rare?

Yes. Castleman disease is considered rare. With about 5,000 new cases annually in the U.S., it is significantly less common than other lymph node disorders, such as lymphoma. Its rarity often leads to delayed diagnosis and confusion with other illnesses.

What Causes Castleman Disease?

The exact cause of Castleman disease remains unknown. In unicentric cases, there are typically no known risk factors. For idiopathic multicentric Castleman disease, researchers suspect that immune system dysfunction, autoimmunity, or viral infections (such as HHV-8) may play a role. Some believe genetic mutations or chronic inflammation may contribute, although Castleman disease is not hereditary and cannot be passed on to others.

Symptoms and Signs

The symptoms vary depending on the type of Castleman disease:

Unicentric Castleman Disease (UCD)

  • Often asymptomatic
  • May present with a single, painless, enlarged lymph node (commonly in the chest, abdomen, or neck)

Multicentric Castleman Disease (MCD)

  • Fever and night sweats
  • Fatigue and weight loss
  • Enlarged liver or spleen (hepatosplenomegaly)
  • Swollen lymph nodes in multiple areas
  • Anemia
  • Nerve damage or peripheral neuropathy (often mild and not painful)
  • Hypoalbuminemia and elevated inflammatory markers like C-reactive protein (CRP)

How is Castleman Disease Diagnosed?

Diagnosing Castleman disease requires a combination of imaging, lab tests, and biopsy:

  • PET scans help identify affected lymph nodes and assess treatment response.
  • Lymph node biopsy is crucial to confirm the diagnosis and distinguish CD from other conditions like lymphoma.
  • Blood tests may show elevated inflammation markers or anemia.

Treatment Options

Treatment depends on the form and severity of the disease:

For Unicentric Castleman Disease:

  • Surgery is the first-line treatment. Removing the affected lymph node typically results in a cure, though recurrence is possible in rare cases.

For Multicentric Castleman Disease:

  • Treatment is more complex and may include:
    • Immunosuppressive therapy
    • Anti-inflammatory medications
    • Antiviral drugs (especially for HHV-8-related cases)
    • Sirolimus, a repurposed transplant drug, discovered by Dr. David Fajgenbaum—a former patient and current researcher—has shown promising results in treating iMCD.

Dr. Fajgenbaum’s work through Every Cure, a nonprofit initiative, has opened new doors in rare disease research by exploring how existing drugs can be repurposed for hard-to-treat conditions like Castleman disease.

Castleman Disease vs. Lymphoma

While both conditions involve lymph node enlargement, there are key differences:

  • Castleman disease usually presents as a solitary lymph node with homogeneous enhancement on imaging.
  • Lymphoma often appears as multiple enlarged nodes and can include moderate enhancement, necrosis, or calcification.

Conclusion

Castleman disease is a rare but serious condition that mimics other illnesses and requires careful diagnosis and tailored treatment. While much remains unknown about its origins, advances in research and treatment—particularly drug repurposing—offer hope for those affected. If you or someone you know is experiencing unexplained lymph node enlargement or systemic symptoms, it’s essential to consult a healthcare provider for a thorough evaluation.

Learn more about ongoing research and support efforts at EveryCure.org
Dr. David Fajgenbaum: https://everycure.org/about/

© 2000-2025 Sieglinde W. Alexander. All writings by Sieglinde W. Alexander have a fife year copy right. Library of Congress Card Number: LCN 00-192742 ISBN: 0-9703195-0-9

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