Introduction

Although it is not classified as cancer, Castleman disease can mimic its effects. It significantly impacts the lymphatic system and immune response. In its multicentric form (MCD), it can lead to widespread issues throughout the body and pose serious health risks. People with HIV should be aware of this. The two conditions often share a common connection through human herpesvirus 8 (HHV-8). Understanding what Castleman disease is and its relationship with HIV can play a crucial role in diagnosing and treating it. This knowledge can improve survival, especially in regions where both conditions are prevalent. 

What is Castleman disease?

Castleman disease is a rare condition where the body's lymph nodes get enlarged, inflamed and sore. The lymph nodes play a crucial role in the immune system. Unlike cancer, it is not a result of uncontrolled cell proliferation. The underlying issue often stems from a dysfunction in the immune system itself. There are two types:^1,2,3

• Unicentric Castleman disease (UCD): affects one group of lymph nodes. It is easy to treat and often includes the removal of affected nodes
• Multicentric Castleman disease (MCD): is a more severe type. It can involve multiple regions of the lymph nodes and has the potential to impact the entire body

The illness poses an even greater risk for people with HIV. Often, a virus known as HHV-8 significantly contributes to the onset of MCD, particularly when the immune system is weakened.

HIV and the hidden trigger: HHV-8

HHV-8 is in the same virus group that can cause cold sores and chickenpox. For the majority of people, it resides within the body and does not produce obvious symptoms of illness. However, for those with HIV, it can manifest in multiple forms. This is particularly the case when their immune system is weakened. When it becomes active, it initiates a series of reactions within the body.^4,5

In the case of MCD, HHV-8 gets into B cells. B cells are a type of white blood cell that helps the body fight viruses, infections and other threats. When these cells have the virus, they make too much interleukin-6 (IL-6). IL-6 is a protein. It is beneficial when it aids in combating diseases, but it is harmful in large amounts. An overproduction of IL-6 leads to the primary symptoms of MCD.^6,7

The symptoms can resemble those of other conditions and progress gradually. Therefore, doctors should consider the possibility of MCD. This disease should be considered an option when people with HIV present with widespread symptoms without an obvious explanation. Blood tests, evaluations of the virus, and analyses of the lymph nodes are crucial. These are utilised to confirm that HHV-8 is responsible for the MCD.⁸

Symptoms

MCD is not quiet, but it is often missed at first. Its signs are not clear and can look like other problems. This is true for people with HIV who may have symptoms for other reasons. One of the first signs is often painless lymph node swelling that does not go away, usually in more than one part of the body. However, there are major symptoms that affect the whole body, including: 

• Unexplained fevers
• Night sweats
• Extreme tiredness
• Unintentional weight loss
• Anaemia
• Large spleen or liver
• Low protein in their blood
• Fluid in their chest or stomach in some people

The challenging aspect is that these symptoms resemble those of other prevalent illnesses seen in people with HIV, such as tuberculosis (TB), certain cancers, or the advanced stages of HIV itself. Consequently, patients might receive treatment or undergo tests for different conditions before a physician considers the possibility of Castleman disease.

Diagnosis

Diagnosing Castleman disease requires a physician to consider it and conduct the appropriate tests. A comprehensive blood test frequently reveals indicators such as elevated C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), alongside low albumin levels, showing that the body is combating a problem. However, the most crucial step is performing a lymph node biopsy. This procedure allows physicians to examine the tissue using a scope. A specific test can determine whether HHV-8 is present in the cells. This is vital for distinguishing it from other conditions. Additionally, assessing the HIV viral load and CD4 count is essential for understanding the overall situation, as a weakened immune system increases the susceptibility to HHV-8-related illnesses.⁸

Treatment options

Managing MCD in people with HIV involves addressing multiple health issues. It requires tackling a challenging cycle of immune impairment, viral reactivation, and ongoing inflammation. However, effective treatment options are now available. These methods can help in managing the conditions and improving the quality of life. Key treatment options include:⁹

• Rituximab: a monoclonal antibody that targets B cells. It is a cancer medication; however, it helps calm the immune system, which is too active and drives MCD
• Antiretroviral therapy (ART): is a combination of drugs that help to keep HIV under control. A low amount of HIV and a stronger immune system mean HHV-8 is less likely to become active again
• Chemotherapy: used for very severe cases or when rituximab is not enough on its own
• IL-6 inhibitors (e.g., siltuximab): treatment used to assist people who lack HHV-8 in their cells. They are also beneficial when there is significant swelling

However, care extends beyond just medications and treatments aimed at specific symptoms. Managing life with both HIV and MCD can seem daunting. People may experience the following symptoms:⁷

• Feeling tired and weak a lot
• Losing weight for no known reason
• Getting sick often or having flare-ups
• Many trips to the hospital
• Stress and not being sure what will happen

That is why a supportive, team-based approach is so important. Support for mental health and emotional well-being is a crucial aspect of care. When identified early and addressed appropriately, many individuals experience significant improvement. They exhibit fewer symptoms of the condition, enhanced immune function, and can return to a more consistent daily routine.⁶

Why it matters: public health and awareness

Castleman disease is rare but severely affects individuals with HIV. It is often overlooked because it mimics other conditions, leading doctors to misdiagnose due to a lack of resources, resulting in:

• Late discovery or no discovery at all
• Misdiagnosing it as tuberculosis, lymphoma, or HIV
• An increased risk of serious complications or mortality 
• Reduced access to life-saving treatments like rituximab 

For those affected, timely diagnosis and treatment can significantly improve their quality of life.¹⁰

FAQs

Is Castleman disease a type of cancer? 

No. Castleman disease is not cancer. But its MCD form can act like it. It can cause swelling in many parts of the body. It is a lymphoproliferative disorder.

How is Castleman disease linked to HIV? 

In people with HIV, a weak immune system activates a virus called HHV-8, which then activates MCD. It gets into immune cells and makes them create too much of a protein called IL-6.

What are the early warning signs of MCD in people with HIV? 

Some of the main signs are:

• Fevers that do not go away
• Night sweats
• Losing weight for no reason
• enlarged lymph nodes in several places
• Feeling very tired and having low red blood cells

Can Castleman disease be cured? 

There is no one cure for every person. However, MCD can be controlled well with the right care. Many people get better with rituximab, ART, and some IL-6 blockers.

Why is it often missed or misdiagnosed? 

Because the signs are the same as other problems linked to HIV. These include tuberculosis, lymphoma, or late-stage HIV.

Summary

Castleman disease is not cancer, but it can have similar effects, particularly impacting the lymphatic system and immune response. It has a multicentric form (MCD) that can cause serious health issues, especially in individuals with HIV, where it is often linked to the virus HHV-8. Understanding the connection between Castleman disease and HIV is essential for diagnosis and treatment. Castleman disease causes lymph nodes to swell and can disrupt the immune system. There are two types: Unicentric Castleman disease (UCD), which affects one group of lymph nodes and is easier to treat, and MCD, which can affect multiple lymph node areas and pose greater risks. In HIV patients, HHV-8 activation can lead to MCD symptoms through an overproduction of interleukin-6 (IL-6). MCD symptoms include persistent painless swollen lymph nodes, unexplained fevers, night sweats, fatigue, unintentional weight loss, and fluid accumulation. These symptoms can overlap with other conditions, making diagnosis challenging.

A thorough examination, including blood tests and lymph node biopsies, is necessary for proper diagnosis. Treatment focuses on managing MCD with options like rituximab, antiretroviral therapy (ART), chemotherapy, and IL-6 inhibitors. Emotional and mental health support is also essential. Early diagnosis can significantly improve the quality of life for individuals affected. Public awareness is crucial to prevent misdiagnoses and improve access to treatment.