Castleman disease: Get informed

What is Castleman disease? 

Definition 

Castleman disease is a disorder causing inflammation of the lymph nodes and lymphatic tissue with the occurrence of benign tumors. It is called a lymphoproliferative disorder, meaning that there is an overgrowth of lymphoid cells, which causes an immune system disorder

First described by Dr. Benjamin Castleman in 1954, Castleman disease is rare. It affects men and women of all ages.

The causes of Castleman disease are relatively unknown, but some studies show a close relationship between it and HHV-8 infection (of the herpes virus subfamily). More generally, people with weakened immune systems (like HIV-positive patients, for example) are more likely to develop this disease.

The impact of Castleman disease on the immune system:

Our immune system is made up of lymph nodes and lymphatic tissue located in the neck, armpits, around the intestines and in the groin (crotch). They ensure that our immune system functions properly. Patients with Castleman disease therefore suffer from immunodeficiency. In addition, they are more likely to develop lymphoma (cancer of the lymphatic system).

The different types of Castleman disease

There are different types of Castleman disease and each has its own method of diagnosis, management and consequences with a different severity index. This is why it is very important to be familiar with all aspects of the disease.

This diversity of types of the disease and its manifestations makes diagnosis often complicated and very time-consuming.

The different forms are classified according to the number of lymph nodes or regions of lymph nodes affected: 

• Unicentric Castleman Disease (UCD) affects only one lymph node group or one lymph node. It is the most common, affecting 50% of cases in the general population. Additionally, it tends to affect children and young adults.
  Multicentric Castleman Disease and Idiopathic MCD (iMCD) affect multiple lymph node regions in the body. The latter is called "idiopathic" because its cause is unknown. It can occur at any age, but mature adults are often the most affected. In total, iMCD accounts for 25% of cases.
• HHV-8 associated Multicentric Castleman Disease (linked to the herpesvirus subfamily) affects adults and accounts for 8-25% of cases.
• There are other more complex and rare forms of Castleman disease but they will not be detailed in this article.

Symptoms

Symptoms of Castleman disease vary according to the type. Patients with UCD are usually asymptomatic, but they do exhibit enlarged lymph nodes (lymphadenopathy). This enlargement is generally not inflammatory or painful, however, when the nodes are very large or "misplaced", they may cause discomfort or pain. 

For patients who have Multicentric Castleman Disease, the symptoms are significantly different:  

• Fever and night sweats
• Fatigue
• Loss of appetite, wasting
• Nausea and vomiting
• Numbness in hands and feet
• Enlargement of liver or spleen
• Rash of red papules on the skin
• Edema (swelling), ascites (accumulation of fluid in the abdomen)
• Kidney failure
• Bruising, easy bleeding, and a risk of infection

Evolution of Castleman disease

Castleman disease is a disorder that, if not properly managed, can lead to a variety of complications ranging from benign tumors that cause minor discomfort, to multisystemic complications that can lead to death.

Diagnosis

Since Castleman Disease is very rare, both patients and doctors often lack awareness and experience, which makes diagnosing the condition complicated. It is important to rely on clinical and biological signs as well as medical imaging. Patients must undergo thorough examinations: a physical examination and a complete blood test.

Diagnosis is based primarily on examination of the lesion (usually one or multiple lymph nodes), for which a biopsy (a minimally invasive surgical removal of a fragment of tissue or organ) is performed. 

Definitive diagnosis remains difficult, in particular for iMCD and can only be made after exclusion of a certain number of tumoral, infectious or inflammatory pathologies and inclusion of a certain number of associated clinical and biological criteria.

Treatments

Existing treatments use a combination of chemotherapy and immunoglobulin (antibody) therapy to destroy abnormal lymphatic cells and reduce symptoms.

The chosen course of treatment depends on the type of Castleman disease:

• For Unicentric Castleman disease, standard treatment consists of surgical removal of the abnormal lymph node or lymph node region (enlarged lymph node). If all of it is removed, definitive recovery is almost certain. It is also important to note that the life expectancy of patients with UCD is not impacted.
  In cases where surgery is not possible or is too invasive, radiotherapy is considered. The results are usually good, but the potential long-term risk must be considered.
• For Idiopathic Multicentric Castleman disease, course of treatment is not yet well defined:
  • In the first line of treatment, 2 biotherapies which target the interleukin-6 pathway (an important role in the inflammatory response) are used: siltuximab which is a monoclonal antibody and tocilizumab which is an IL-6 anti-receptor. These two treatments are effective in most patients, particularly in treating general symptoms and inflammatory syndrome. However, they are less effective for Kaposi's sarcoma.
  • As a second line of treatment, conventional anti-inflammatory (corticosteroids) and immunosuppressive treatments (sirolimus, cyclosporine, rituximab) are an option.
  • As a last resort, treatments targeting cytokines and inflammatory cellular pathways (bortezomib, thalidomide, anakinra) are considered.

Prognosis remains cautious and highly dependent on complications and response to treatment, but median life expectancy remains above 10 years in 70% of cases.

• For cases of HIV negative HHV-8 associated Castleman disease, standard treatment consists of an anti-B cell monoclonal antibody, rituximab, which is equivalent to chemotherapy. Relapses are possible, but patients may be responsive to the same treatment again. The prognosis here is clouded by the risk of developing non-Hodgkin's lymphoma. The median survival expectancy at 10 years is at around 50%.
• For cases of HIV positive HHV-8 associated Castleman disease, treatment is also based on rituximab. However, there are reservations about the use of this therapy.  It is the most aggressive form of Castleman disease, and mortality remains high, although it has been declining in recent years. The median survival expectancy remains below 50% at 10 years.

Living with Castleman disease

Castleman disease results in a variety of symptoms that can be hard on patients. These symptoms can have an impact on their social and professional life. Intense fatigue, nausea, night sweats, and chronic pain can make daily life difficult for patients. Some treatments can relieve their nausea and chronic pain, but they must learn to live with latent fatigue.

In the majority of cases, stomach upsets accompanied by pain, vomiting and nausea are observed, which generally leads to loss of appetite and weight loss. This is why it is very important to eat healthily. You can find tips and symptoms to watch out for in the article "Living with Castleman disease" to learn how to live better with CD.

I have Castleman disease

If you have Castleman disease or are close to a patient with Castleman disease, there are certainly many questions you may be asking yourself. Sometimes, sharing experiences with people who are also affected by Castleman disease can help with the follow-up and management of the disease as well as with the advancement of medical research. Carenity is a social network adapted to your needs where you can share your opinion on your care and treatment through online surveys and polls. You can also connect and exchange in our discussion groups with other people affected by CD to feel less alone in the face of this illness.

Sources:

https://member.carenity.us/magazine/news-from-the-media/living-with-castleman-disease-554 
https://member.carenity.us/magazine/news/castleman-disease-everything-you-need-to-know-542 
https://castleman.fr/diagnostic-et-classification-de-la-maladie/  
https://cdcn.org/castleman-disease/faq/  
https://www.has-sante.fr/upload/docs/application/pdf/2019-11/pnds_castleman_2019.pdf  
Article: “International, evidence-based consensus treatment guidelines for idiopathic multicentric Castleman disease” from the American Society of Hematology’s Blood journal
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6238190/ 

Published Sep 2, 2020