Introduction

We’ve all been there. It’s flu season and you’ve caught a cold. As your body fights off infection, your lymph nodes start to swell. It can be a pretty painful experience for just a few days, but imagine experiencing it every day.

What is Castleman disease?

First described in 1954 by Benjamin Castleman, Castleman disease (CD) is a condition characterised by the unregulated enlargement of lymph nodes.^1,2

CD is categorised into two main types. They are:¹

• Unicentric CD (UCD): one or more lymph nodes appear in a single region of the body
• Multicentric CD (MCD): lymph nodes grow in multiple sites
  • POEMS-MCD: a form of CD that presents with cell death in the peripheral nervous system, endocrine diseases, enlarged organs, skin conditions and excess myeloma protein in the blood
  • HHV-8+MCD: in which the condition is brought on by the presence of human herpes virus (HHV)
  • iMCD: where the causation of MC is unknown or idiopathic

Global incidence rates of CD are difficult to track due to its rarity. However, there are 6500-7700 new cases per year in the United States. UCD is typically diagnosed in people in their forties, while all types of MCD become prevalent in people in their 50s to 70s. 

While UCD does not seem to be influenced by biological sex, MCD appears to be more common in people assigned male at birth (AMAB). Additionally, data concerning any ethnic predisposition for CD varies, with one UK study notably positing that the majority of patients were not Caucasian.³

Main symptoms of Castleman disease

Despite presenting in distinct subcategories, CD’s overarching symptom is the discomfort caused by the swelling of the lymph nodes. However, some UCD patients can actually be asymptomatic.³

MCD typically has these symptoms:³

• Fever, night sweats, swelling throughout the body, uncontrolled weight loss
• Enlarged liver or spleen (this is typically observed in POEMS or iMCD)
• System dysfunctions
  • Renal: seen in HHV-8+ MCD and iMCD
  • Liver: seen in HHV-8+ MCD and iMCD
  • POEMS-MCD has its own presenting symptoms (see above) 

What causes Castleman disease?

The exact cause of CD remains unclear. However, each subtype has its own proposed underlying mechanisms.

What causes UCD?

Current research suggests that UCD is a neoplastic condition. This means it is caused by an abnormal growth of tissue. The additional cells are ‘monoclonal’, meaning that they all come from one cell.⁴

What causes POEMS-CD?

Also considered to be caused by monoclonal processes, POEMS-CD is promoted by plasma cells that produce cytokines. Cytokines are signalling proteins responsible for moderating many of our bodies’ processes. Specifically, a cytokine called Vascular Endothelial Growth Factor (VEGF) has been linked to POEMS-CD and is known for its pro-inflammatory activity.⁴

What causes HHV-8+CD?

Another cytokine, called interleukin-6 (IL-6), has been strongly linked to HHV-8+CD, which is believed to be caused by viral infection. HHV-8 is commonly linked to HIV positivity, meaning people who are HIV immunocompromised may be more likely to develop HHV-8+CD. Human herpes virus causes the release of the viral cytokine IL-6 (vIL-6), which in turn is linked to pro-inflammatory processes.^5,6

Treating Castleman disease

There is currently no cure for CD. However, many treatment options are available. Most prominently, surgery is proposed to remove lymph nodes in all forms of CD. Chemotherapy, stem cell transplants and antibodies that target IL-6 are also offered to treat MCD. Lately, antivirals are prescribed to treat HHV-8+MCD.⁷

Beyond the symptoms

While treating CD can be an effective means of improving the quality of life of those affected, there is a pertinent psychological strain faced by people with CD. The permanence of the condition is an emotional experience.

Common issues associated with Castleman disease

The compressive symptoms of CD tend to disrupt daily activities due to their painful nature. Additionally, the intensity and uncertainty of the diagnostic process can cause excess stress in both people with CD and their loved ones. The routine procedures, such as bone marrow biopsies and chemotherapy, have been described as a “daily struggle” by parents.

Due to the diversity of the condition, some people may experience extreme fatigue and nausea, while others experience severe pain. Ultimately, the mental health concerns for people living with CD are substantial. Surveys have found the condition to have a moderate to severe impact on iMCD patients’ emotional well-being, fiscal health, ability to carry out independent tasks and socialisation. The severity of MCD also poses a mortality risk to people with the condition, further enhancing the stressors associated with treatment and health. With no established cure, even with the removal of lymph nodes via surgery and symptom management, there remains the threat of CD recurrence. 

Indeed, the variance in presenting symptoms can result in the need for caregivers, which can subsequently lead to its own complications. The surveys mentioned above also made note of the need for relocation and the emotional toll suffered by caregivers.^3,8,9

A personal perspective

CD most commonly manifests in people aged 40 or over. The unpredictable occurrence in otherwise healthy individuals can prove to be a difficult transitional experience. One male living with the condition recalled being “knocked down” by iMCD.³ What’s more, external conditions like commuting long distances for treatments can place additional strain on people with CD. 

The information gap regarding CD remains substantial, with data on life expectancy being significantly skewed. One patient was told he only had two years left to live by a doctor who had not previously heard of the condition. It’s easy to empathise with the panic and grief that accompany such a serious diagnosis, especially when limited research leaves many questions unanswered for prospective patients.¹⁰

These feelings of stress, confusion, grief and turmoil can often lead to people with CD feeling isolated and experiencing serious psychological distress. It highlights the need for greater research into the condition, so that people currently experiencing it can access the answers and support they deserve.

Organisations like the Castleman Disease Collaborative Network offer support and advice for both patients and caregivers while also promoting further research into CD.

Summary

Castleman disease is a rare, complex disorder. Depending on their specific symptoms (which are determined by the subtype of CD), people with CD can suffer severe emotional distress brought on by physical pains, fatigue and nausea. They may also experience further psychological distress when confronted by the permanence of their condition, often feeling helpless and unable to socialise. 

Caregivers for those with CD are also likely to fall victim to the challenges posed by CD, as they often sacrifice parts of their own lives to care for loved ones. As such, CD can be described as an all-encompassing condition, having a primarily physical impact which causes secondary (yet still pertinent) emotional and psychological suffering. 

FAQs

What is Castleman disease?

Castleman disease (CD) is a rare condition that causes the swelling of our lymph nodes in one or multiple parts of our body.

How can I recognise the symptoms?

Common symptoms include pain resulting from the swelling, fevers, night sweats, weight loss, inflammation and enlarged organs.

How is it treated?

Surgery is the main method to remove lymph nodes, but some patients may need antiviral medications or chemotherapy to treat the underlying causes.

What are some of the complications associated with Castleman disease?

The sudden onset of the condition can cause confusion and fear in many people. Additionally, the daily fatigue and physical pain can cause emotional distress due to a loss of mobility or difficulty completing daily tasks we may take for granted.