Chronic active Esptein-Barr virus disease (CAEBV) is a lymphoproliferative disorder (“lympho” = lymphocytes, a type of white blood cells, “proliferative” = excessive cell growth).^1,2 CAEBV is characterised by the uncontrolled growth of Epstein-Barr virus (EBV)-infected lymphocytes, specifically T cells or NK cells that fight infection.³

CAEBV is caused by Epstein-Barr virus (EBV) infection.^1-9 EBV is a common virus which infects most people and usually doesn’t cause any symptoms. However, in some individuals, the virus infects their T or NK cells, affecting their immune function. This disrupts the immune system, and the body fails to suppress the EBV infection, leading to the development of CAEBV.^2,4 These abnormal EBV-infected cells grow uncontrollably, and can affect multiple organs in the body, leading to organ dysfunction and other life-threatening complications.^1-4

CAEBV is initially recognised as a childhood disease, it is now recognised that CAEBV can affect adults too.⁵

Synonyms: chronic active EBV infection, chronic EBV infection syndrome, CAEBV syndrome, CEBV, immunodeficiency 32b, IMD32B, systemic chronic active EBV (CAEBV) disease.^5-8

CAEBV is one of the “Epstein-Barr virus–positive T-cell/NK-cell lymphoproliferative disorders of childhood”. This group of disorders include 4 major conditions that are also caused by EBV – hydroa vacciniforme lymphoproliferative disorders, severe mosquito bite allergy, CAEBV, and systemic EBV-positive T cell lymphoma of childhood. Further classification and definition of CAEBV can be found at The International Consensus Classification of Mature Lymphoid Neoplasms: a report from the Clinical Advisory Committee (published in 2022).

Universal rare disease classifications provide a common language for recording, reporting and monitoring diseases. Please visit the Rare Disease Classifications page for more information about these internationally recognised classifications.

ORPHA:2566 Chronic Epstein-Barr virus infection syndrome

There is currently no known ICD-11 classification for this condition.

The symptoms and severity of CAEBV may vary between individuals.⁴ CAEBV is a progressive condition, which means that the symptoms worsen over time.^2,4

Common symptoms of CAEBV include fever, sore throat, swollen lymph nodes, enlarged liver and/or spleen, anaemia, thrombocytopenia (low platelet count), diarrhea, and skin rash.^2,4,5,8,9, These symptoms are similar to that of infectious mononucleosis, and are commonly referred to as infectious mononucleosis-like symptoms.

In some individuals with CAEBV, they progressively develop immunodeficiency (weakened immune system), which makes them more vulnerable to other infections.⁴ Individuals with CAEBV can develop other potentially life-threatening complications such as interstitial pneumonia, myocarditis, vasculitis, hemophagocytic lymphohistiocytosis (HLH), and malignant lymphoma and leukemia.^2,4,5,8,9

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

Rare diseases are often serious and progressive, exhibiting a high degree of symptom complexity, leading to significant disability. Majority of the estimated two million Australians living with a rare disease meet the Australian Government’s definition for disability (in accordance to the Australian Public Service Commission and Australian Bureau of Statistics), and many experience severe and permanent disability impacts. If you or someone you care for is experiencing disability-related impacts from a rare condition, please speak with a health or disability professional for advice. Information about relevant disability support can be found at the RARE Portal’s Disability Support Information page.

CAEBV is caused by Epstein-Barr virus (EBV) infection.^1-9 EBV is a virus that is often found in most people but does not cause any symptoms (ubiquitous).⁴ It is not yet fully understood why EBV infection causes CAEBV in some individuals.^3,7 It is suggested that a combination of genetic factors, variation in EBV strains, and environmental factors contribute to the development of CAEBV.^2,8

Diagnosis of CAEBV may be made based on:^2,8

• physical examination of the symptoms
• medical history
• blood tests showing a high level of EBV in the blood or tissue
• biopsy (usually of the liver or lymph node) to determine which types of immune cells are affected (T or NK cells)

More information on the international diagnostic criteria can be found at Updated guidelines for chronic active Esptein-Barr virus disease (published in 2023).

A differential diagnosis can rule out other conditions that have similar symptoms, such as hydroa vacciniforme lymphoproliferative disorders, severe mosquito bite allergy, systemic EBV-positive T cell lymphoma of childhood, severe EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH), extranodal NK/T-cell lymphoma, aggressive NK-cell leukemia.²

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

Haematopoietic stem cell transplant may be curative treatment option for CAEBV, however it may not be suitable for everyone and risks include side effects and complications.^2-4 Other treatments are targeted at reducing the amount of virus in the body and managing symptoms. These may include chemotherapy and medications to help regulate the immune system.⁵

Please speak to your medical team to learn more about the possible treatment or management options for your condition. Treatment will depend on an individual’s specific condition and symptoms. It is also important to stay connected to your medical team so that you can be made aware of any upcoming clinical trial opportunities.

Healthcare professionals involved in the care of individuals with CAEBV may include general practitioners (GP), paediatricians, infectious diseases specialists, clinical pathologists, haematologists, immunologists and oncologists. The need for different healthcare professionals may change over a person’s lifetime and extend beyond those listed here.

Clinical care for rare diseases often involves a multidisciplinary team of medical, care and support professionals. Please note that the information provided here is as a guide and that RVA does not necessarily monitor or endorse specific clinics or health experts.

For many rare diseases, palliative care services may be relevant and useful. Palliative care services are available for people (adults, children and their families) living with a life-limiting illness and is not only for end-of-life care. It can also help at any stage of illness from diagnosis onwards, and will look different for different people. Palliative care services provide assistance, support, resources and tools to help people manage their illness and the symptoms, ease pain, and improve comfort and quality of life. If this is relevant to you and you wish to find out more information about palliative care and how it can help you, please visit:

• Australian Institute of Health and Welfare: Palliative care Overview
• Australian Government Department of Health, Disability and Ageing: Palliative care
• Palliative Care Australia

We are not aware of any clinical care guidelines for CAEBV 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:

• Updated guidelines for chronic active Epstein-Barr virus disease developed by medical experts and the Committee for Guidelines for the Management of Chronic Active EBV Disease, Related Disorders (the MHLW Research Team in Japan) for diagnosis and treatment of CAEBV, published in 2023.

Individuals living with rare diseases may have complex medical issues and disabilities, which are not always visible. It is often useful to refer to their medical history as well as personal information such as a medical card, doctor’s letter, or if available, a rare disease passport, for relevant information.

In addition, individuals, their parents, families and carers often develop extensive expertise on their specific rare disease. It is important to recognise that they can contribute valuable knowledge about their rare condition. Rare diseases often impact individuals differently, so it’s important to consider a person’s lived experience.

There are specific considerations around participating in rare disease research, including clinical trials. It is important to be mindful of issues such as data privacy, research ethics, consent and differences in research regulations between Australia and other countries. For more information, please visit the RARE Portal’s Considerations for Participating in Health and Medical Research page.

If you are interested in finding clinical trials for your condition, please visit the following websites; however, there may not be any clinical trials available:

• Australian Clinical Trials
• ClinicalTrials.gov

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

We are not aware of any rare disease organisations for CAEBV in Australia or internationally. If you know of any rare disease organisation supporting people living with CAEBV, please let us know via the Contribute page. If you are interested in starting an Australian organisation, please see Engaged, Ethical and Effective: A Guide for Rare Disease Organisation Leaders in Australia.

Please note that RVA does not monitor or endorse each group/organisation’s operational governance and activities. When engaging with a group, please consider the information on the RARE Portal’s Finding Helpful Peer and Community Supports page.

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

If you would like to share your personal story with RVA, please visit the Rare Voices Australia: Share Your Story page. RVA will consider your story for publishing on our website and inclusion on the RARE Portal.

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.

People living with a rare disease often face unique challenges such as diagnostic delays, misdiagnoses, limited treatment options, and limited access to rare disease specialists and support. These challenges may impact people’s emotional wellbeing and quality of life. Many find it helpful to seek mental health and wellbeing support to cope with ongoing stress and uncertainty. Connecting with people who have shared experiences through a support group may also be helpful. Information about relevant mental health and wellbeing support can be found at:

• Mental Health and Wellbeing Support for Australians Living with a Rare Disease
• The National and State Services pages underneath the ‘Mental Health’ sections listed

Further information on CAEBV and EBV can be found at:

• Genetic and Rare Diseases (GARD) Information Center: Immunodeficiency 32B
• National Organization for Rare Disorders (NORD): Immunodeficiency 32B
• Centers for Disease Control and Prevention (CDC): About Epstein-Barr Virus

Online Mendelian Inheritance in Man (OMIM): #226990 Immunodeficiency 32B; IMD32B

Orphanet: Chronic Esptein-Barr virus infection syndrome

This page has been developed by Rare Voices Australia (RVA)’s RARE Portal team.

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.