Introduction

Castleman Disease (CD) is a group of very rare disorders affecting lymph nodes around the body. It can present itself in ways similar to some types of cancer, and can be difficult to diagnose correctly on first inspection.¹ As this is such a rare condition, there hasn’t been a lot of research and work put into finding out the mechanisms of the disease, and beneficial treatments are very few and far between. In the past 70 years since the disease was discovered, some progress has been made in understanding the pathology behind the disease as well as learning about the different sub-types, and how they are best treated. 

The discovery of Castleman Disease

Castleman Disease was first discovered in 1954 by a doctor, Benjamin Castleman, when he had a patient with troubling symptoms that didn’t fit any known logical explanation. The first patient and case study seemed to have an enlarged mass in his chest, that wasn’t explained by any other conditions like cancer or immunological issues, and so the doctor needed to do some more research and intensive investigations on the patient.² From this point, those presenting with lymph node enlargement and other unknown masses can be assessed for other signs of CD as well as other conditions. 

In the 1980s, the disorder was divided into two main subtypes, unicentric CD (UCD) and multicentric CD (MCD). This was because the number of enlarged lymph nodes frequently differed between patients, some having only one enlargement (UCD) and others having many enlargements (MCD).³ This was further divided into more subtypes of the disease in later years as links to certain viruses began to come to light. In the 1990s, it was discovered that the herpes-human virus 8 (HHV-8) was linked to many cases of the MCD type. This is the same virus that is linked to Kaposi’s sarcoma, the rare type of cancer seen in severely immunocompromised people, most commonly HIV.⁴

Background information

Overall, males have a slightly higher risk of developing MCD than females, and the most common age groups for development of both conditions are between the 4th and 6th decades, however CDcan occur in all ages, including young children.⁵ There are no definitive risk factors for the development of the condition, however there have been close links to chronic viral hepatitis, organ transplantation, men who have sex with men (MSM) and consanguinity.

Typically, CD presents with either singular or multiple localised masses in the lymph node regions. Alongside this, a confusing mixture of very broad symptoms can occur, including a high fever of unknown origin, general fatigue and lethargy, skin rashes and night sweats to name a few.⁶ As many different diseases can present with fevers, the guidelines state that all other common causes of this, including infection, must be excluded first before a diagnosis of CD is made. Other conditions can also occur alongside CD, including autoimmune myasthenia gravis and psoriasis.⁷

Overtime, scientists and doctors have developed ways in which to investigate and diagnose cases of CD. Presently, contrast enhanced CT scans, looking at enlarged lymph nodes as well as their shape, are often used to assess the severity and type of condition. After looking at many different cases of the disease, they were also able to use a specialised branch of medicine, known as histology, to find different subtypes of the conditions, and discover how exactly the disease progresses with time.⁸ Positively, the 5 year survival rate for the UCD type is 100% and for the MCD type is around 50-77% and there are some, albeit limited treatment options available. These typically include surgical removal of the affected lymph nodes as a first line treatment option, however, this isn't always feasible. More treatment options are being explored however, they are still few and far between.⁶

Future planning

In the past several decades, since CD was first discovered, little has been done to move medical knowledge forward. There are a few doctors and scientists who are actively campaigning to increase public awareness of the condition and, with that, increase the research and funding into adequate treatments. In 2012, the Castleman Disease Collaborative Network was founded, which has led to great progress in the world of CD, further leading to the first new FDA approved medication in the 21st century, and also fresh guidelines for diagnosis and treatment.⁹ This is a step in a positive direction in America and will hopefully be replicated in other areas of the world in the coming years.

Summary

Castleman Disease has had quite a long and unrelenting journey in the world of medicine. In more recent years, knowledge on how to efficiently diagnose and treat the disease has vastly improved, and the condition is being more widely recognised in mainstream medicine. Further research is needed, however, in order to improve the understanding of how this condition develops, including the risk factors involved in this. 

FAQ’s

When was Castleman Disease first discovered?

 In 1954, a doctor called Benjamin Castleman first discovered the condition that he coined as ‘Castleman Disease’ when one of his patients presented with a singular enlarged mass in his chest, not in keeping with any of the usual diagnoses. From this time, many more cases have been found, and the initial condition of Castleman Disease has been expanded to include some of the newer found subtypes. 

What are the subtypes of Castleman Disease?

There have been two reported subtypes of Castleman Disease so far, unicentric (UCD) and multicentric (MCD). These were found when scientists looked closer at the extracted lymph nodes under microscopes and in scans of the patients, and found that some cases had only one enlarged lymph node, whereas others had multiple enlarged nodes. The criteria was set for these in the 1990s.