Erdheim-Chester Disease

Erdheim-Chester disease is a rare form of non-Langerhans cell histiocytosis.

It involves the excessive production of histiocytes, which are a type of white blood cell. These cells, which normally help fight infection and injury, then gather in different organs and tissues and can result in a variety of symptoms, including organ failure.

Erdheim-Chester is a disease that most often becomes apparent in middle age, with an average age at onset of 53 years. It can affect men and women. The rate of occurrence is not known, although it is believed to be under-diagnosed and/or misdiagnosed. At the present time, it is not categorized as a cancer, immune disorder, or infection. It is not believed to be contagious or hereditary. The cause is not known.

The first two cases of ECD were reported by scientists Jakob Erdheim and William Chester in 1930. In 1972, Dr. Ronald Jaffe reported a third case and coined the name Erdheim-Chester disease (ECD).

This disease mostly affects long bones (arms and legs), but it can occur in the tissues behind the eyeballs, kidney, skin, brain, lung, heart, pituitary gland, and a part of the posterior abdominal wall called the retroperitoneum. Erdheim-Chester is sometimes mistaken for Langerhans cell histiocytosis. However, a biopsy of the affected tissue differs in a number of ways from LCH and can establish a definite diagnosis. The cells in ECD stain for the same proteins as JXG but the clinical presentation and age is different. The symptoms and course of the disease depend on the location and extent of the involvement of the internal organs (i.e. the disease outside the bones).

Because this is a very rare disease, no large studies have been performed, and no treatment plan has been established that is widely accepted. However, various treatments have been used with limited success. These include steroids, immunotherapy (treatment to restore the ability of the immune system such as interferon), chemotherapy to control the over-production of cells, the use of high-energy rays (radiation therapy), and/or surgery. While these treatments may control the symptoms and growth of the disease, there is no known “cure.”

Erdheim Chester can be life-threatening with complications such as heart failure, severe damage to the lungs, and kidney failure. However, with treatment, there are patients who are able to live a near-normal life.

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Symptoms

Erdheim-Chester can involve many different systems in the body and most often affects the long bones. In order of frequency, it also occurs in the kidney, retroperitoneum, skin, brain, lung, tissue behind the eyes, pituitary gland, and heart. The following symptoms may indicate disease involvement but are not necessarily diagnostic. The disease varies greatly from patient to patient, and some but not all of these symptoms may be present.

  • Bone (usually long bones of the legs and arms but also knees, shins, ankles, arms, and rarely in the lower jaw, facial bones, and spinal column)
    Pain - this may be specific to one area or more widespread, sometimes associated with muscle pain
  • Kidney
    Lower back pain, reduced kidney function/painful or difficult urination
  • Retroperitoneum (a part of the internal abdominal wall)
    Abdominal or lower back pain, painful or difficult urination
  • Skin/Eyelids
    Rash or soft, fatty, yellow bumps
  • Brain (brain stem and cerebellum)
    Difficulty with coordination, staggering gait, slurred speech, behavior disorders, and rapid, involuntary eye movement (nystagmus). Diabetes insipidus is common
  • Lung
    Dry cough, shortness of breath with exercise
  • Eyes (tissue behind the eyes/eyelids)
    Pain and redness, bulging eyes, difficulty with vision including double vision, yellow bumps on the eyelids
  • Pituitary gland (diabetes insipidus)
    Excessive thirst and urination
  • Heart
    Shortness of breath, fatigue, and swelling of feet, ankles, and lower legs
  • Additional Symptoms
    Weight loss, fever, muscle and joint aches, night sweats, weakness/fatigue, and increased tendency to get infections

Involvement of more than one system is not uncommon. While the long bones are the most frequently affected sites, more than 50% of patients have involvement in other parts of the body. Lung symptoms are due to progressive scarring and thickening of the lung tissue and can affect the ability of the heart to pump enough blood to the lungs and the rest of the body. Diabetes insipidus is believed to occur in 30% of patients. ECD of the heart causes problems when histiocytes accumulate in the valves or heart muscle and affect the heart’s ability to pump blood through the arteries.

It is important to remember that symptoms alone do not diagnose ECD. Thus, it is important to consult a physician to receive an appropriate workup and accurate diagnosis.

Diagnosis and Treatment

Because it is so rare, Erdheim-Chester disease is often difficult to diagnose. Patients may go for months and even years after symptoms start until they are properly diagnosed. This disease is sometimes mistaken for Langerhans cell histiocytosis, and a thorough workup including biopsy is necessary to tell the difference between the two diseases. There are also differences in the appearance of the bone lesions on x-ray, but x-ray alone is not diagnostic.

A biopsy involves taking a small piece of the affected tissue so that it can be viewed under a microscope by a pathologist. If the cells in the tissue have specific characteristics, the diagnosis of ECD can be made. One of these characteristics is the presence of foamy histiocytosis with signs of inflammation and something called Touton-type giant cells. Unlike LCH, the cells in Erdheim-Chester disease do not have Birbeck granules or stain positively for something called the S-100 antigen or CD1a. ECD cells stains positively for the same proteins as JXG, that is CD68 and factor XIIIa.

Once the diagnosis is made, the extent of disease should be established. Further diagnostic testing will depend on the individual case and may include testing similar to that used for Langerhans cell histiocytosis:

  • Physical examination, history of symptoms, past illnesses, etc.
  • Blood tests: To evaluate function of the internal organs such as heart and kidneys.
  • Neurological examination: Testing of ability to walk, muscle testing, coordination, etc.
  • X-ray: This can be performed of the lungs or the bones to determine if there are abnormalities.
  • Bone scan: This is a type of x-ray that looks for bone lesions. A small amount of radioactive material is injected into a vein, collects in any abnormal parts of the bones, and is shown on a scanner.
  • CT scan: This is an x-ray that takes a number of detailed pictures at different angles inside the body. Dye may be injected into a vein or swallowed to help find any abnormalities.
  • MRI: This is another kind of x-ray that takes a number of detailed pictures inside the body. A substance called gadolinium may be injected into a vein.
  • PET scan: A small amount of radioactive sugar is injected into a vein, and diseased cells show up brighter on the scanner.
  • Ultrasound: This is a kind of x-ray procedure where high-energy sound waves are bounced off organs and tissue and make echoes, which form a picture of the internal body.
  • Electrocardiogram: This is a tracing of the heart rate and rhythm.
  • Echocardiogram: This uses sounds waves to provide pictures of the heart in order to evaluate blood flow and heart function.
    The severity of the disease is determined by how widespread the involvement occurs outside of bone and whether internal organs are affected.

Because this is a very rare disease, no large studies have been performed, and no treatment plan has been established that is widely accepted. However, various treatments have been used by individual doctors with different levels of success. These include:

  • Systemic corticosteroids
    A kind of drug based on hormones that work to reduce inflammation in the body.
  • Immunotherapy
    The purpose of this treatment, also known as interferon, is to restore the ability of the immune system to fight off infections. It is usually given as an injection.
  • Chemotherapy

Drugs usually given in the vein to control the over-production of histiocytes. This may include vinblastine (Velban), vincristine (Oncovin), cyclophosphamide (Cytoxan), doxorubicin (Adriamycin), and cladribine (2CdA). Other drugs such as methotrexate, Gleevec, Tamoxifen, Imuran, and CellCept have also been used. New therapies which target the chemicals (cytokines) produced in excessive amounts in patients with ECD have been tested in a very small number of patients with ECD and may prove beneficial in the future but would be considered experimental at present.

  • Radiation
    This involves the use of high-energy rays to destroy rapidly increasing histiocytes.
  • Surgery
    This may be used to decrease symptoms caused by masses of histiocytes.

It is important to remember that while these treatments may control the symptoms and growth of the disease, to date, there is no known “cure” for Erdheim-Chester.

FAQ

What causes Erdheim-Chester Disease (ECD)?

Erdheim Chester disease involves the excessive production of histiocytes, which are a type of white blood cell. What causes these cells to over-produce is not yet known.

Is there a cure for Erdheim-Chester Disease?

The best treatments available today may control and sometimes shrink the tumors associated with the disease. However, we usually don’t use the term “cure” for this disease, since no specific amount of time without active disease has been established to determine that a patient is cured.

What are the different therapies/treatments commonly used to treat Erdheim-Chester Disease?

To date, there is no universally accepted treatment for Erdheim Chester. Various treatments, however, have been used with different levels of success. These include steroids, interferon, radiation, surgery, and chemotherapy such as vinblastine, vincristine, Cytoxan (cyclophosphamide), Adriamycin (doxorubicin), and 2CdA (cladribine). Other drugs have also been used.

Can an infant be tested at birth for ECD?

A biopsy of the affected tissue, rather than a blood test, is required for diagnosis and would therefore not be appropriate as a routine test unless this disease is suspected.

What are the possible side effects of interferon?

More common signs/symptoms include:

  • Flu-like symptoms (Fever, chills, headache, dizziness, fatigue, muscle aches, nausea, vomiting, diarrhea)
  • Irritability/depressionDecreased appetite
  • Irregular heart rate
  • Decreased blood counts (red cells, white cells, and clotting cells)
  • Liver abnormalities
What are the possible side effects of 2-CdA (cladribine/leustatin)?

More common signs/symptoms include:

  • Flu-like symptoms (Fever, chills, headache, fatigue, nausea/vomiting)
  • Decreased appetite
  • Constipation
  • Low blood counts (red cells, white cells, and clotting cells)
  • Skin rash/redness/itching

What Do I Do Now?

A new diagnosis of a histiocytic disorder can bring feelings of being overwhelmed, bewildered, scared, angry, sad, disappointed, helpless, and sometimes even feelings of guilt.  It is a time filled with unknowns, change, and new people and situations.  Most parents feel ill-equipped to understand what is happening to their child and how to navigate through the illness to recovery.  There are, however, strategies and resources that can help you, your child, and other family members get through the uncertain times that lie ahead. One step at a time, you can gather information, create a support system, learn how to cope with stress, and become a strong advocate for your Histio Warrior as part of the medical team. The following tips and suggestions are provided to help guide you through this journey toward your Histio Warrior's good health.

Choosing a Doctor

Histiocytosis can be considered a systemic illness; especially in cases where the disease is found in more than one system within the body.  Some patients and caregivers may prefer to consult several specialists, depending on the different locations of symptoms.  In this case, it is helpful to have one physician coordinate your care.  An oncologist is usually the most appropriate choice.

Make sure that your doctor is someone you can trust and with whom you can communicate.  Important qualities to look for in a doctor are:

  • feeling as though you are heard,
  • being given the opportunity to ask questions, and
  • feeling respected.

If you are unsure about your physician, it is reasonable to schedule another appointment to discuss your concerns. While it is ideal to find a physician experienced and knowledgeable about histiocytic disorders, it is not always possible to find one who is nearby. If this is the case, ask the physician if he/she is open to a consultation with a knowledgeable physician and is willing to learn more about the disease. The Histiocytosis Association maintains a listing of doctors in a Physician Directory who have are knowledgeable about histiocytosis. You may also call us at +1 856-589-6606 for help finding other physicians in your area or for more information.

Call your insurance company to find out whether your plan will cover visits to the physician you are considering. Oftentimes a Team Social Worker and/or the hospital financial counselor can help smooth out insurance problems. Ask for help from a trusted friend if you feel overwhelmed in dealing with insurance issues.

Sharing Information

Talking with your child:  If your child is old enough to understand, sharing information can help him/her build trust in both you and his/her/your medical caregivers.  It can also help your child cooperate with treatment and become a part of his/her/your medical team.

  1. Use words and ideas that are appropriate for your child’s age. 
  2. Share information at a level that is in keeping with his/her ability to understand.
  3. Use your child’s questions as a guide to what he/she wants to know. 
  4. Encourage your child to talk about his/her fears and concerns. 
  5. Remind your child how much you love him/her.

If you are uncertain about how to talk to your child, your healthcare team can be of assistance.

Talking with family and friends:  In the days and weeks following diagnosis, extended family and friends will need to be notified and periodically updated.  However, explaining your situation multiple times can be exhausting and time-consuming. The Association offers a private Facebook group to help connect you with others. Some patients and families find that journaling is therapeutic and can provide an easy way to track their history and progress.

Talking with your child’s siblings:  When your child is diagnosed with a histiocytic disorder, everyone in the family is affected, including brothers and sisters. They may feel anxious, lonely, resentful about the attention their sibling is getting, guilty about being healthy, or even responsible for the illness.

  1. Give information that is appropriate for your child’s age.
  2. Explain that no one did anything to cause the illness, and reassure them that it is not contagious. 
  3. Give them a chance to talk about how the illness is affecting them or you.  Be willing to answer questions. 
  4. Remember that it will be easy for them to feel overlooked and unimportant, so it will be important to show that you love them and are proud of them.

Talking with your child’s school:  Contact your school principal/counselor regarding your child’s diagnosis or if your diagnosis may affect your child. You may want to take brochures and other basic information about your histiocytic disorder. If your child is the patient, provide a written description of the health needs, such as what medications may need to be given at school, dosages, and times, signed by your physician.  (Some schools will provide the form to be filled out and signed by your child’s physician.)  Ask for a plan to take care of your child’s needs at school.  You may need to provide written permission for the school to communicate with your physician, in case of an emergency.

Getting Organized

Appointments:  A calendar is a useful tool for remembering appointments and planning for changes to your established schedule.  Calendars that show a week at a time also provide room on each day to record additional brief notes and reminders.

Medical Information:  While some basic medical notes can be kept in a calendar, some patients and parents may choose to enter medical information in a laptop or keep a separate notebook.  Be sure to date all entries.  This information will be especially helpful when a new or different caregiver is involved.  Examples that you may want to keep track of include:

  1. Results of various tests.
  2. A listing of allergies.
  3. A listing of medications and dosages. 
  4. Names and phone numbers of your medical care team.  
  5. Health information, such as your hospital number, social security number, and insurance information.
  6. Records of what was discussed during a medical visit/phone conversation and by whom.
  7. Notation of changing symptoms.

Adults may find it helpful to collect and organize medical records, starting as soon as possible after diagnosis.  Although the original reports must remain in the physician or hospital file, you are legally entitled to copies of your records. You must submit a signed request for each physician’s office and the hospital.  By keeping all records in one place, you can easily share these with other health care providers that you may see in the future. Follow this link to read more about obtaining your medical records.

Insurance

If you have health insurance, it’s important that you know what your plan covers.  Read your policy carefully to understand the health and medical services covered. Find out the portion of medical expenses you'll be responsible for paying. When you have questions or there are things you don’t understand, reach out to other experts available to you, such as the human resources personnel at your place of employment or financial counselors at your medical treatment center.  If filing and tracking claims feels overwhelming, you may want to ask a trusted friend or relative to assist in managing your insurance issues. 

When you call the insurance company, ask to work with one case manager. This may help simplify the process by having one person that knows your needs and can manage your claims. If possible, communicate with the same person on an ongoing basis.  Remember to keep a journal of all encounters. 

If you don’t have health insurance, if coverage is not adequate, or if you are not able to get insurance because of your pre-existing condition, you may qualify for your state’s high-risk insurance pool. You can obtain more information about whether your state participates at the National Association of State Comprehensive Health Insurance Plans website.  If your state does not participate, you may qualify for the federal high-risk insurance pool.  For more information, contact the U.S. Department of Health and Human Services.

Creating a Support Network

Online:  You can subscribe for our emails and you will  receive important announcements regarding the latest information on the histiocytic disorders.   The Association also maintains a Facebook page for families and patients with this disease. 

Local support:  The hospital where you or your child is being treated may have a support group for patients or parents of children with histiocytic disorders, rare diseases in general, or even cancer.  Establishing face-to-face relationships with others going through similar experiences can be helpful.

The Association sponsors patient and family Regional meetings, which are held in various locations around the U.S. and hosted by Association staff and volunteers. They are a good opportunity to meet other families and patients, learn from expert physicians, receive and give emotional support, and share practical coping skills while also providing a time to relax, knowing you are with people who understand.

Fundraising events for histiocytic disorders are another way to make connections with families in your region.  A listing of dates and fundraising events is provided on the Upcoming Events page.

Virtual opportunities to connect are also available.

Educate Yourself

Self-education about histiocytic disorders is an important part of advocating for your and your child.  It will help you to make informed decisions about care and play a more active role in recovery.

The Association website provides education on a number of topics, including disease information, family resources, and past and ongoing research projects.  The Histio Resource Directory provides an extensive listing of global, national, and state-by-state resources for patients and families.  Some of the resources listed are informational, while others are service-based.  A listing of past and current research projects funded by the Association can be found on the Grant Awards page, providing a glimpse into the past trends and current progress of research into the histiocytic disorders.  The Disease Information section of the website features detailed, reliable information on all of the histiocytic disorders.  This can be printed out and shared with medical caregivers, family, and friends if needed.

The Internet is a good source of information about histiocytosis and the treatment options, but the amount of information can be overwhelming, and the information is not always reliable. Some of it, in fact, is inaccurate.  Reliable information is more likely to be found in more current documents that are free of grammatical and spelling errors, appear to be objective, are free of advertisements, and clearly state their sources.

Advocating for You or Your Child

It is essential to take an active role in your or your child’s health care.  However, many patients and caregivers have little experience being advocates when they first receive a rare disease diganosis. The following is a list of essential tips for becoming a successful advocate:

  1. Learn about the diagnosed type of histiocytosis and become acquainted with the basic medical terms.  Knowledge is empowerment.
  1. Know the warning signs that mean you may need emergency help.
  2. Know who to call in case of an emergency, and keep phone numbers handy.
  3. Keep a list of healthcare members involved in your medical care, along with contact information.
  4. If possible, take a companion (family member or friend) along on important medical appointments.  The companion can help with remembering details of what was said and may assist by taking notes.
  5. Write down your questions before entering appointments or meetings and write down further questions as you think of them during the meeting.  Don’t be afraid to ask these questions.  This will be an important step in beginning to understand more about the disease.  Medical information is often confusing and the language used by medical professionals is not easily understood, especially during stress.  Whenever someone uses a word that you don’t understand, stop the conversation for a minute and ask the person to explain. 
  6. Keep a healthcare notebook with a listing of allergies, medications, symptoms, and communications with healthcare providers.
  7. Find out about resources that the hospital provides, such as a social worker or patient representative.  They can often assist with transportation costs, temporary housing if needed, parking fees, insurance issues, counseling, and other services. 
  1. Be persistent in getting the care you feel that you or your child needs.  Don’t hesitate to ask for what you need, and if you do not feel responded to, ask again or ask someone who will respond. 

Trust your intuition.  It can be a powerful decision-making tool.  You know yourself or your child better than anyone else.

Self Care

Being sick or caring for a sick child/loved one can be stressful and may take a toll on your physical and emotional health. Recognizing your own needs for support, help, health, and comfort can be difficult when you’re focused on the needs of others, but it’s important to remember that caring for yourself is essential.  When your needs are taken care of, your loved ones will also benefit.  Give yourself time for regular physical activity and rest.  Pay attention to signs of stress, and consult your physician if you need further help.

Printable Fact Sheets

Learn more about the different types of histiocytic disorders from these helpful fact sheets. Printing these for family and friends is a quick and easy way to teach them about the disease. More extensive information can be found in the Disease Information section of our website.

Choose from the following Fact Sheets:

Histiocytic Disorders Overall FAQ

What are histiocytic disorders, and how are they classified?

Histiocytic disorders are a diverse group of diseases caused by over-production of white blood cells known as histiocytes, which can lead to organ damage and tumor formation. They include a wide variety of conditions that can affect both children and adults.

The disorders are classified into three groups based on the types of histiocyte cells involved.

  • The first group is called a dendritic cell disorder, and the most common disease in this group is Langerhans cell histiocytosis. Also included in this group are more rare diseases, juvenile xanthogranuloma (JXG) and Erdheim Chester.
  • The second group is called a macrophage cell disorder, and includes primarily hemophagocytic lymphohistiocytosis (HLH) and Rosai-Dorfman.
  • The third group is called malignant histiocytosis and includes certain kinds of leukemia and tumors.
Why are all of these diseases with different names considered to be related to each other?

All of the diseases are caused by the over-production of white blood cells called histiocytes. Their different classifications depend on the type of histiocyte involved.

Where can I find reliable information about histiocytosis?

The Histiocytosis Association’s online community provides a number of informational documents and articles, as well as links to medical articles about the histiocytic disorders. While the Internet does provide a significant volume of information about histiocytic disorders, some of this information is not accurate. It is important to look for documents that are current, are free of grammatical and spelling errors, appear to be objective, are free of advertisements, and clearly state their sources.

How can I explain histiocytosis to family and friends?

Histiocytosis is a rare disease that is caused by the over-production of a type of white cell that can lead to organ damage and the formation of tumors. The Histiocytosis Association’s Disease Fact Sheets are also a great way to help explain these complicated diseases to family and friends.

What is an orphan disease?

According to the Rare Disease Act of 2002, an orphan disease, also known as a rare disease, affects less than 200,000 persons in the U.S., or less than 1 in 1500 people. The criteria may vary in other countries. For example in Europe, an orphan disease is defined to occur in less than 1 in 2000.

How many orphan diseases are there?

According to the National Institutes of Health there are approximately 6800 such diseases. Combined, they affect nearly 30 million Americans.

Where can I learn more about rare diseases in general?