HHV-8 associated Multicentric Castleman Disease (HHV8+MCD)

Diseases of the Immune System

HHV-8 associated Multicentric Castleman Disease (HHV8+MCD)

Rare Disease Classifications:

ORPHA:570438 HHV-8-associated multicentric Castleman disease

ICD-11: 4B2Y Other specified disorders involving the immune system

IMPORTANT INFORMATION

The information on the Rare Awareness Rare Education (RARE) Portal is intended for educational purposes only and does not replace professional advice.

Rare diseases typically display a high level of symptom complexity and variability. Individuals diagnosed with the same rare disease may be impacted differently and each person’s experience is unique. Please seek support from qualified healthcare professionals to learn more about the most suitable care and support options for you.

There are currently no known organisations in Australia specifically for this rare disease. If you know of any rare disease organisation/s supporting people living with Castleman disease, please let us know via the Contribute page. If you are interested in starting an Australian organisation for people living with Castleman disease, please see Engaged, Ethical and Effective: A Guide for Rare Disease Organisation Leaders in Australia.

If you are aware of any additional information that may benefit stakeholders with an interest in this page, or if you notice any broken links or inaccurate information, please let us know via the Contribute page.

Emergency Management

There may be special considerations for the emergency management of individuals living with Castleman disease presenting to emergency departments.

Clinical Care Guidelines

We are not aware of any clinical care guidelines for Castleman disease in Australia. If you know of any relevant care guidelines, please let us know via the Contribute page.

The following guidance is available from international experts outside Australia; however, there may be information that is not relevant or applicable to the Australian context, and may not be up to date:

The management of Castleman disease – a ‘Good Practice Paper’ containing recommendations where there is limited evidence but a degree of consensus or uniformity is likely to be beneficial to patient care; compiled according to the British Society for Haematology (BSH) process and published in 2021
International, evidence-based consensus diagnostic criteria for HHV-8–negative/idiopathic multicentric Castleman disease(iMCD); published in 2016 by a working group of 34 experts in iMCD and related disorders from 8 countries (including 2 physicians that are also iMCD patients)

Synonyms

Human herpesvirus-8-associated multicentric Castleman disease, Castleman disease, CD, multicentric Castleman disease, MCD, angiofollicular lymph node hyperplasia, angiomatous lymphoid, angiofollicular ganglionic hyperplasia, Castleman tumour, giant benign lymphoma, giant lymph node hyperplasia, hamartoma of the lymphatics

Summary

KSVH/HHV-associated multicentric Castleman disease (HHV8+MCD) is a type of Castleman disease where multiple lymph nodes throughout the body become enlarged and overactive due to a Human herpesvirus 8 (HHV-8) infection.^1-3 Lymph nodes are part of the immune system and are the home base of immune cells. There are hundreds of lymph nodes in the human body. In HHV8+MCD, there is an overproduction of immune cells as well as signalling proteins (cytokines). These immune cells and proteins cause inflammation and damage the body. The signs of HHV8+MCD can have a slow and subtle onset or be sudden and life threatening.

Below are other types of Castleman disease that are not caused by Human herpesvirus 8 (HHV-8) infection.^2,4,5 The different types of Castleman disease have overlapping symptoms but different complications, causes, and treatment methods.

Unicentric Castleman disease – affects only one or a cluster of lymph nodes
Idiopathic multicentric Castleman disease – affects multiple lymph nodes similar to HHV8+MCD, but the cause is unknown
POEMS-associated multicentric Castleman disease (POEMS-MCD) – associated with part of POEMS syndrome

Castleman Disease subtypes

Useful Links for Professionals

Orphanet: Castleman Disease

Personal Stories

Castleman disease varies between individuals, and each person’s experience is unique.

If you would like to share your personal story with Rare Voices Australia and have it included on the RARE Portal, please visit Rare Voices Australia: Share Your Story.

Symptoms

Symptoms of KSHV/HHV8-associated multicentric Castleman disease (HHV8+MCD) may have a slow and subtle onset or may begin suddenly and require urgent emergency care. The most common symptoms include:^1-4

enlarged lymph nodes/lumps under the skin in more than one place
flu-like symptoms which may include aches, pains, tiredness, night sweats, weight loss, appetite loss, or nausea
spotted red or purple skin rash (cherry hemangioma or violaceous papules)
swelling or enlargement of any part of the abdomen or organs (oedema/ascites)
tingling or numbness in the hands or feet (peripheral neuropathy)
difficulty breathing

HHV8+MCD can progress to multi-system organ failure with symptoms that vary depending on the specific organs impacted. Individuals with HHV8+MCD also have an increased risk of developing lymphoma (cancer of the lymph nodes) and Kaposi sarcoma (cancer in the skin, mouth, stomach, intestines or anus).^4,6

Please speak to your medical team to learn more about the symptoms and complications of Castleman disease.

Cause/Inheritance

KSHV/HHV-8-associated multicentric Castleman disease (HHV8+MCD) is caused by Kaposi’s sarcoma-associated herpesvirus (KSHV) also known as Human herpesvirus 8 (HHV-8) infection.^1,4,5 The HHV8 virus reproduces itself in lymph nodes and causes an over-production of immune proteins (such as CD20 and interleukin-6) and immune cells. HHV-8 MCD usually occurs in individuals that are immunosuppressed, such as individuals with human immunodeficiency virus (HIV) or another immune deficiency, as their immune systems are unable to control the HHV-8 virus; however, not all immunosuppressed individuals with HHV-8 will develop Castleman disease.

Diagnosis

Diagnosis of KSHV/HHV8-associated multicentric Castleman disease (HHV8+MCD) may be made based on the results of an excisional lymph node biopsy and blood and urine tests.⁵

An excisional lymph node biopsy involves the removal of the entire lymph node (either whilst awake under local anaesthetic or asleep using general aesthetic). The lymph node is then examined under a microscope to look for the characteristic changes that are associated with Castleman disease. A computerised tomography (CT) or positron emission tomography–computed tomography (PET-CT) scan is often performed to look for the presence of other affected lymph nodes in order to differentiate between multicentric Castleman disease (multiple affected lymph nodes) and unicentric Castleman disease (UCD) (only one or one cluster of affected lymph node).^5,6

Blood and urine tests may be performed to look for other signs of HHV8+MCD such as:^1,⁶

presence of Kaposi’s sarcoma-associated herpesvirus (KSHV)/Human herpesvirus 8 (HHV-8)
anaemia (low amount of red blood cells)
high inflammatory markers in blood (such as CRP and/or ESR)
protein and blood cells in urine which can indicate kidney disease
high number of platelets (clotting agent in blood)
high globulins and low albumin levels in blood
high levels of plasma cells in bone marrow and lymph nodes

Differential diagnosis (to rule out other conditions) includes unicentric Castleman disease, POEMS-associated multicentric Castleman disease, idiopathic multicentric Castleman disease, Hodgkin lymphoma, non-Hodgkin lymphoma, systemic lupus erythematous, rheumatoid arthritis and other autoimmune diseases, and acute viral infections including Epstein–Barr virus.^2,4-6

Please speak to your medical team to learn more about the available diagnostic pathways for Castleman Disease.

Treatment

There is no curative treatment for KSHV/HHV-8 associated multicentric Castleman disease (HHV8+MCD); however, symptoms can be managed by biological medications that control the number of lymphocytes (a type of immune/blood cell) in the body.^5,6 In some cases, antiviral medications and/or chemotherapy may also be used. Other types of medications may also be used to treat associated complications on a case-by-case basis. Individuals with HIV do not have to stop their HIV treatments in order to treat their HHV8+MCD.

It is best to speak with your medical team to learn more about possible treatments for HHV8+MCD and to determine suitability of treatment. Treatment will depend on an individual’s specific symptoms and complications.

Clinical Care

Healthcare professionals involved in the treatment of Castleman disease may include general practitioners (GP), paediatricians, haematologists, pulmonologist, nephrologists and oncologists.^2,6,10 The need for different healthcare professionals may change over a person’s lifetime and extend beyond those listed here.

Research and Data

Castleman Disease Collaborative Network: Physicians & Researchers has information on relevant research and resources for Castleman disease.

Please visit Australian Clinical Trials to learn about clinical trials for Castleman disease in Australia; there may not be any clinical trials currently available.

Information regarding clinical trials for Castleman disease in other countries can be found at ClinicalTrials.gov; there may not be any clinical trials currently available.

It is best to discuss your interest in any clinical trials with your medical team to determine suitability and eligibility.

Rare Disease Organisation(s)

There are currently no known organisations for Castleman disease in Australia. If you are aware of any Castleman disease organisations in Australia, please let us know via the Contribute page.

Global organisations
Castleman Disease Collaborative Network
Website: https://cdcn.org/
Contact form: https://cdcn.org/contact/

The Castleman Disease Collaborative Network (CDCN) is an organisation focused on improving the understanding, diagnosis, and treatment of Castleman disease. They provide information about the disease, promote research, facilitate collaboration among scientists and clinicians, and provide support to patients and families affected by Castleman disease.

Please note that RVA does not necessarily monitor or endorse each group/organisation’s operational governance.

For information on available government and social services that provide support for individuals with a rare disease, please visit the National and State Services pages.

Mental Health

Please visit the ‘Mental Health’ sections listed on the National and State Services pages.

Other

Further information on Castleman Disease can be found at:

References

National Organization for Rare Diseases. Castleman Disease. Published 1988-2022. Updated 16 June 2022. Accessed 21 August 2024. https://rarediseases.org/rare-diseases/castlemans-disease
Castleman Disease Collaborative Network. Accessed 10 August 2024. https://cdcn.org/castleman-disease/
Orphanet. Castleman disease. Accessed 20 August 2024. https://www.orpha.net/en/disease/detail/160
Fajgenbaum DC, Uldrick TS, Bagg A, et al. International, evidence-based consensus diagnostic criteria for HHV-8–negative/idiopathic multicentric Castleman disease. Blood. 2017;129(12):1646-57. https://doi.org/10.1182/blood-2016-10-746933
Carbone A, Borok M, Damania B, et al. Castleman disease. Nature Reviews Disease Primers. 2021;7(1):84. https://doi.org/10.1038/s41572-021-00317-7
Lomas OC, Streetly M, Pratt G, Cavet J, Royston D, Schey S, et al. The management of Castleman disease. British Journal of Haematology. 2021;195(3):328-37. https://doi.org/10.1111/bjh.17688
Genetic and Rare Disease Information Centre. Castleman Disease. Updated July 2024. Accessed 21 August 2024. https://rarediseases.info.nih.gov/diseases/12656/castleman-disease

Page Last Updated

26/09/2024 14:18

Diseases of the Immune System