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Disease Profile

Multicentric Castleman Disease

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

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ICD-10

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Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

MCD; Plasmablastic multicentric Castleman disease; PMCD;

Categories

Blood Diseases; Rare Cancers; Viral infections

Summary

Multicentric Castleman disease (MCD) is a rare disease that affects the lymph nodes and related tissues. It is a form of Castleman disease that is "systemic" and involves multiple regions of lymph nodes (as opposed to unicentric Castleman disease, which involves a single lymph node or single region of lymph nodes). The signs and symptoms of MCD are often nonspecific, and are mild in some people but life-threatening in others.[1][2] Symptoms may include enlarged lymph nodes in multiple regions, fever, weight loss, nausea, rash, and/or an enlarged large liver and spleen.[1][2] The disease is diagnosed based on the symptoms present, laboratory test results, imaging studies, and results of a biopsy of the lymph nodes which shows specific features when studied under the microscope.[1] In some cases, MCD is caused by human herpesvirus-8 (HHV-8) and is referred to as HHV-8-associated MCD. In other cases, the cause is not known and it is referred to as HHV-8 negative MCD, or idiopathic MCD (iMCD).[1][2] Treatment of MCD is challenging, and treatment options and outcomes depend on the type and severity in each person.[2]

Symptoms

The signs and symptoms of multicentric Castleman disease (MCD) are often nonspecific and blamed on other, more common conditions. They can vary but may include:[3][4][5]

  • Fever
  • Enlarged lymph nodes
  • Night sweats
  • Loss of appetite and weight loss
  • Weakness and fatigue
  • Shortness of breath
  • Nausea and vomiting
  • Enlarged liver or spleen
  • Peripheral neuropathy
  • Skin abnormalities such as rashes and/or pemphigus

Less commonly (<10% of cases), people affected by MCD will have no signs or symptoms of the condition.[4]

Other conditions associated with MCD include amyloidosis, POEMS syndrome, autoimmune disease, hemolytic anemia, and immune thrombocytopenic purpura (ITP).[4]

Cause

In about half of people with multicentric Castleman disease (MCD), it is caused by human herpesvirus-8 (HHV-8), in which case it is called HHV-8-associated MCD.[1][2] This type of MCD usually occurs in people with human immunodeficiency virus (HIV) or a weakened immune system due to other reasons, because the weakened immune system is not able to manage a HHV-8 infection.[1] It is thought that the infection multiplies in the lymph nodes, leading to the release of high levels of inflammatory chemicals (particularly cytokines such as interleukin-6), causing the specific symptoms of MCD.[6]

In the remaining half of cases of MCD, the cause is not known, in which case it is called HHV-8 negative MCD, or idiopathic MCD (iMCD).[1][2] Possible factors that have been speculated to play a role in causing iMCD include being infected with a virus other than HHV-8, acquiring a genetic mutation that signals the release of substances that lead to the disease, inheriting a genetic mutation that predisposes a person to developing the disease, and autoimmunity (when the body's immune system mistakenly attacks healthy tissues).[1][6] People with iMCD often also have high levels of cytokines, but the cause of their increased production in iMCD is not yet known.[6]

Diagnosis

The signs and symptoms of multicentric Castleman disease (MCD) are often nonspecific and blamed on other, more common conditions. However, if MCD is suspected, the following tests may be recommended to help establish the diagnosis and rule out other conditions that cause similar features:[4][5]

  • Blood tests can be ordered to evaluate the levels of Interleukin-6 (IL-6) and other substances in the body, which can be elevated in people with MCD. They can also be helpful in ruling out other autoimmune conditions and infections that are associated with similar signs and symptoms
  • Imaging studies (such as a CT scan, PET scan, MRI scan, and/or ultrasound) can help identify enlarged lymph node(s) and other health problems
  • A biopsy of affected tissue, often a lymph node, is usually recommended to confirm the diagnosis

Treatment

Treatment of multicentric Castleman disease (MCD) is challenging, and no single treatment works for all people with the disease.[7] Treatment options may depend on the type of MCD (HHV-8-associated or idiopathic) as well as the severity of symptoms.

HHV-8-associated MCD is typically initially treated with rituximab to fight against immune cells called B lymphocytes. This treatment is reportedly highly effective for HHV-8-associated MCD. Antiviral medications (particularly for those with HIV) and/or chemotherapy may also be recommended.[1]

Idiopathic MCD (iMCD) is typically initially treated with siltuximab or tocilizumab (which aim to control activity of interleukin-6) with or without corticosteroids. Unfortunately, about half of people do not improve with these therapies. In those with only mild symptoms, rituximab may be an alternative option for initial treatment. In very severe cases, adjuvant combination chemotherapy is also recommended. Other types of therapies may be recommended if the above therapies are not effective.[2]

FDA-Approved Treatments

The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

    Organizations Providing General Support

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

      • The American Cancer Society provides detailed information about Multicentric Castleman Disease. Click on the link to access this information.
      • The Castleman Disease Collaborative Network, a global initiative dedicated to accelerating research and treatment for Castleman disease, provides information about Multicentric Castleman Disease.
      • Mayo Clinic has an information page on Multicentric Castleman Disease.
      • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

        In-Depth Information

        • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss Multicentric Castleman Disease. Click on the link to view a sample search on this topic.

          References

          1. Castleman Disease. National Organization for Rare Disorders (NORD). 2017; https://rarediseases.org/rare-diseases/castlemans-disease/.
          2. van Rhee F, Voorhees P, Dispenzieri A, et al. International, evidence-based consensus treatment guidelines for idiopathic multicentric Castleman disease. Blood. September 4, 2018; [Epub ahead of print]:https://www.ncbi.nlm.nih.gov/pubmed/30181172.
          3. Castleman disease. Mayo Clinic. August 2014; https://www.mayoclinic.org/diseases-conditions/castleman-disease/basics/definition/con-20031703?p=1.
          4. Neetu Radhakrishnan, MD. Castleman Disease. Medscape Reference. January 2015; https://emedicine.medscape.com/article/2219018-overview.
          5. Jon C Aster, MD; Jennifer R Brown, MD, PhD; Nikhil C Munshi, MD. Multicentric Castleman's disease. UpToDate. January 2015; Accessed 6/25/2015.
          6. About Castleman Disease. Castleman Disease Collaborative Network (CDCN). https://www.cdcn.org/about-castleman-disease. Accessed 11/6/2018.
          7. Treatment of Multicentric Castleman Disease. American Cancer Society. January 12, 2017; https://www.cancer.org/cancer/castleman-disease/treating.html.

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