What is Erdheim-Chester Disease?
What is ECD Symptoms Signs Tests Diagnosis
Differential Diagnosis ECD Suspicion? Treatment Print View
Erdheim-Chester Disease is an extremely rare disorder that can affect many different organs of the body. It is characterized by excessive production and accumulation of specific cells whose normal function is to fight infections. These cells, which are called histiocytes, accumulate in the loose connective tissue of the body. As a result this tissue becomes thickened, dense and fibrotic. Multiple different organs can be affected. Unless successful treatment is found, organ failure can result.
Erdheim-Chester Disease usually affects adults and the cause is unknown. It is not currently categorized as a cancer, infection or auto-immune disease. It has not been found to be contagious or genetic in nature. It can affect both men and women.
Disease involvement may include long bones of the legs and arms, skin, tissues behind the eyeballs, lungs, brain, pituitary gland, kidney, abdominal cavity, the membrane surrounding the heart, adrenal glands and more rarely other organs. Each patient can have a different combination of organs attacked.
ECD is considered one of the histiocytic diseases and is often described as a rare multi-system, non-Langerhans Cell histiocytosis.
There have been a very limited number of published cases of ECD in the world since it was first described in the literature in 1930 by the American pathologist, William Chester. Most published articles on ECD are anecdotal in nature as the disease is so rare, studies on groups of patients is extremely difficult. Because it is so rare and because it is not discussed in the common textbooks of medicine, many doctors have never heard of it. It is also considered difficult to diagnose. For these reasons some feel the disease could be under-diagnosed and may not be quite as rare as thought.
What are some Symptoms of Erdheim-Chester Disease?
ECD symptoms depend on which organ(s) is involved, which varies with each patient. For this reason, the symptoms of ECD will also vary with each patient. Only a doctor can diagnose ECD, but some of the more common symptoms might include:
· Bone pain in the long bones of the legs and arms on both sides (bilateral). Leg pain occurs most often in the knees, shins and ankles. Arm pain is most often in the upper arms. More than 50% of ECD patients share this symptom, but it is important to note some patients never have bone pain symptoms.
· General symptoms of weight loss; fever; night sweats; muscle and joint aches; feeling of discomfort, weakness, and fatigue (malaise); flu-like symptoms that linger or continue to return
· Excessive thirst and urination (diabetes insipidus)
· Balance issues; difficulty walking (ataxia); slurred speech (dysarthria); involuntary, rapid eye movements (nystagmus)
· Lower back, flank or abdominal pain, often associated with kidney issues (retroperitoneal fibrosis); reduced kidney function
· Bulging of the eye (exophthalmos)
· Vision difficulties. These may include bilateral fluttering in the peripheral vision, double vision, reduced vision or other vision disturbances.
· Sore or bump under the skin (xanthomas), rash
· Shortness of breath (dyspnea)
· Increased susceptibility to infections
A single patient may have a different combination of these symptoms, along with others. This is partly what makes ECD so difficult to diagnose. By taking a systemic view of symptoms it may be possible to test for and diagnose ECD earlier. This will potentially give patients the best chance for a successful treatment plan.
What are some Signs of Erdheim-Chester Disease?
A sign is different from a symptom. Whereas a patient is aware of a symptom, they may very well not be aware of a sign. A sign is an objective finding by a physician, usually during an examination.
Signs associated with ECD are the result of histiocytic cell infiltration of various tissues. Depending on the organ involved, some of the following signs might be found:
·
Bilateral symmetric
medullary sclerosis with cortical thickening and coarsened trabecular pattern of
the long tubular bones of the extremities is the most common sign of ECD.
This means the bone marrow has an increased density, with a thicker than normal
outside layer, usually found in the long bones of the legs and arms on both
sides of the body. This is most often observed when the physician reviews xrays
and bone scans. Typically, this is the most common presenting sign of ECD.
·
Abnormal lipid
metabolism.
This means the cholesterol readings are not within the normal range. This is
discovered by doing a blood test.
·
Moderate anemia.
This means there is a low number of healthy red blood cells that deliver oxygen
to the tissues in the body. This is discovered by doing a blood test.
·
Increased C-reactive
protein and erythrocyte sedimentation rates.
This implies there is an inflammatory condition occurring somewhere within the
body. This is discovered by doing a blood test.
·
High creatinine.
Creatinine is a measure of kidney function. To have a high creatinine indicates
the kidneys are not functioning properly. This is discovered by doing a blood
test. (High blood pressure (hypertension) is often associated with kidney
issues.)
·
Interstitial lung
disease involving accumulations of histiocytic cells and fibrosis in a
predominantly perilymphangitic and subpleural pattern.
Other findings may
include patchy centrilobular ground glass opacities.
This means there is
swelling and scaring of the deep lung tissue in a particular pattern. This is
normally found with an xray, CT scan or MRI.
·
Infiltration of the
retroconal fat and optic nerve sheath to large retrobulbar, intraconal masses.
This means a doctor has found something irregular about the eyes. This can be
something small or a large mass in the area behind the eye. This is normally
found with a CT or MRI scan.
·
Cardiac issues which
might include one of the following: diffuse periaortic fibrosis (also known as
"coated aorta"); pericardial infiltration with pericardial effusion; myocardial
infiltration; atrial pseudotumour; or aortic and mitral valve disease.
This means there is abnormal tissue in or around the heart. The aorta is the
great artery that comes from the left ventricle of the heart. A “coated aorta”,
or periaortic fibrosis, implies there is abnormal, thickened dense tissue
surrounding the aorta. The pericardium is the sac that contains the heart and
the base of the major arteries and veins attached to the heart. Pericardial
effusion means there is excess fluid in the pericardium. Myocardial is the
actual heart muscle so myocardial infiltration means there is abnormal tissue
growth within the actual heart muscle. Atrial pseudotumour means there is an
enlargement in the upper chambers of the heart that appears to look like a
tumor. The aortic and mitral valves are two of the four valves found in the
heart. Valve disease is when these valves do not function properly in keeping
the blood flowing properly through the heart. These signs are most often seen
when doing an echocardiogram.
·
Issues with teeth and
jaw bones
ECD has been reported in the medical literature to cause degeneration of bone
tissue, including those of the upper and/or lower jaw. Evidence of ECD has also
been reported in the tissue that surrounds and supports the teeth. In addition,
some patients have found they experience difficulty with tooth enamel "chipping
off" or tooth "erosion". Dental examinations are needed to identify any of
these issues.
·
Soft tissue masses
and/or lesions
This means there is an
area of abnormal tissue. This is usually found with an xray, CT scan or MRI.
These might appear anywhere in the body. Sometimes the abdominal area may not
show masses, but indicate fat stranding
A single patient is unlikely to experience all of these signs. Rather, the particular signs found will depend on what organs are involved with ECD.
What Tests Might be Used to Diagnose and/or Monitor ECD?
As a doctor tries to diagnose and understand the cause of the symptoms and signs of ECD, the following tests might be ordered:
· X-Rays
· Electrocardiogram (EKG or ECG)
How is Erdheim-Chester Disease Diagnosed?
It is often difficult to diagnose ECD. Many patients go years before they get a correct diagnosis. When a doctor learns of suggestive symptoms (s)he will often order more tests. X-Rays and/or electrocardiograms (EKG or ECG) are often the initial tests. Non-invasive scans such as CT scan, CT/PET scan, MRI, bone scan, or echocardiogram may be warranted depending on the symptoms, clinical signs and/or results from previous tests. If the results of these scans are concerning, a doctor will most likely be interested in obtaining a biopsy.
If a mass or lesion is found within the body, a tissue biopsy might be performed. A pathologist will study the tissue sample that is obtained via the biopsy. ECD affected tissue will usually contain clusters of lipid-laden, foamy histiocytes with signs of chronic inflammation and Touton-type giant cells, fibrosis and possible fat necrosis. The pathologist will study the tissue sample further and find the histiocytes expressing CD68 positive, CD1a negative, with S-100 protein expression variable and without Birbeck granules.
A bone biopsy might be warranted. If ECD has affected the bones, the bone biopsy will typically show sclerotic bone.
Although brain lesions are sometimes seen with ECD, it is not always possible to perform a biopsy on these lesions depending on where they appear in the brain. Doctors will normally see these lesions when an MRI of the brain is performed. These lesions will show T2 hyperintensity and often intense gadolinium enhancement. The lesions most often occur in the pons and cerebellum. These findings might be confused with multiple sclerosis as they mimic a demyelinating process as normally seen in multiple sclerosis.
What Other Diseases Might be Included in the Differential Diagnosis?
Because ECD is so difficult to diagnose, it is often important to know what other diseases might be considered while trying to reach a diagnosis. The following diseases can sometimes have symptoms and signs that closely resemble ECD. Only a doctor can provide a correct diagnosis.
· Endocrinological symptoms
· Hypophysitis
·
Kidney Disease / Kidney Failure
(often idiopathic for ECD patients) -
Kidney support group can be found at
http://www.kidney.org/ )
· Langerhans’s cell histiocytosis (see also www.histio.org )
· Lymphoma
· Malignancies (particularly lymphoma)
· Metabolic disorders
· Retroperitoneal Fibrosis or Ormond’s Disease ( See also RPF strong support group website at at http://health.groups.yahoo.com/group/Retroperitoneal_Fibrosis/ )
· Thyroid abnormalities
Because the symptoms of ECD are unspecific, the number of differential diagnoses is large. The above list is not exhaustive.
What Should You Do if You Suspect You or Someone You Know May Have a Rare Disease Such as ECD?
See your doctor. You may need to educate your doctor(s) about some rare diseases and ECD specifically. It is likely that a diagnosis of ECD (and rare disease in general) will require a broad range of sophisticated tests and several specialists. You may need to be persistent. It may take seeing several different doctors before you find one who knows much about ECD. If you need help in finding a doctor who is knowledgeable about ECD, please select "Physicians" on the menu or contact us at support@erdheim-chester.org.
It is important that the patient and the caregiver be actively involved in the diagnostic and treatment process, taking care to retain accurate records and especially ensuring that the purpose and risks associated with each of the tests required are understood by both you and the specialists. If in doubt, seek another opinion, as many as you need, until you find the answers you need.
How is Erdheim-Chester Disease Treated?
To date, there is no "cure" for ECD. The best treatments available today control and sometimes shrink the growths associated with the disease. The limited evidence available suggests that if treatment is stopped the growths will return, usually quickly. Consequently a successful treatment may be on-going indefinitely.
Because of the rarity of this disease, clinical trials have not been conducted. This means there is no treatment plan that has been scientifically tested. It is also likely that a range of treatments is required because of differences between patients.
For these reasons, there is not a treatment plan that is accepted by the medical community as the "best available". However, there are a number of doctors who have documented their findings with a particular treatment plan. These are considered treatment plans based on anecdotal experience. They include:
·
Immunotherapy (Interferon)
Interferon is a
protein the body creates when it is trying to fight off a foreign agent such as
a virus. If a doctor believes this is the best course of action for a patient
(s)he will prescribe the medicine to the patient and continue monitoring the
patient for any adverse side effects. With interferon treatment a patient is
given the medicine by injection (shot), usually 3 times a week, for extended
periods. It is a treatment that can be given in the home (much like an insulin
shot); the patient usually does not need to go into a doctor’s office or
hospital to obtain the injection. The patient may experience some side effects
such as fatigue (flu-like feelings). However, for some patients these side
effects diminish with time. (For more information about interferon
treatment for ECD, go to the Technical Papers webpage and see “Discussion
Regarding ECD with Dr. Julien Haroche Sept. 17, 2008” and
“Discussion
Regarding ECD with Dr. Razelle Kurzrock July 16, 2008”).
·
Systemic
corticosteroids
Corticosteroids are
hormones that are produced in the body as a response to stress, foreign bodies,
inflammation, etc. An often used corticosteroid is prednisone. If a doctor
believes corticosteroids are a good course of action for a patient, (s)he will
prescribe the medicine to the patient and continue monitoring the patient for
any adverse side effects. Corticosteroids are often taken orally (by mouth)
daily. The patient may experience some side effects that should be closely
monitored by a doctor. For more information about corticosteroids, see
http://en.wikipedia.org/wiki/Corticosteroid
).
·
Chemotherapy (vinblastine,
vincristine,
cyclophosphamide ,
doxorubicin,
cladribine)
Sometimes a doctor
will make the decision that chemotherapy is the best way to treat ECD in a
particular patient. Chemotherapy means that a chemical is used to kill certain
cells in the body in an attempt to fight off a disease. There are a number of
chemotherapy drugs (see above list) that have been used in the fight against ECD.
One that seems to be used with some frequency is cladribine (or CD2a). This
drug is usually used for a specific period of time. All chemotherapy treatments
must be given with close monitoring by a doctor. For more information about
chemotherapy, see
http://en.wikipedia.org/wiki/Chemotherapy
).
·
Immunosuppressants
In some
cases an immunosuppressant drug , such as
azathrioprine(Imuran)
or
mycophenolic acid (Cellcept), may be used as part of the treatment plan for ECD. These are most
often taken orally under the close monitoring of a doctor. Immunosuppressants
reduce efficacy of the immune system requiring patients on this form of
treatment to be extra careful about reducing risk of infections. For more
information about immunosuppressant therapy, see
http://en.wikipedia.org/wiki/Immunosuppression ).
·
Surgical debulking
If a mass has formed
as the result of ECD, a doctor may recommend removing as much of the mass as
practical using surgical techniques. This is done with the intent to allow
other treatments to work more effectively and/or to improve the quality of life
where a reduction in mass size may help to reduce symptoms. The decision
regarding surgical debulking is done by a doctor on a case-by-case basis.
·
Radiation treatment
Sometimes a doctor may
try to treat a mass using radiation techniques. Radiation treatment is done in
a hospital or clinical setting. For more information about radiation
treatments, see
http://en.wikipedia.org/wiki/Radiation_therapy
)
·
Combination treatment
of
Inflixomab(Remicade),
Methotrexate, and
Micophenolic Acid (Cellcept)
has been used in at least one patient
The results of this treatment have not been documented as of yet. If an ECD
patient and/or treating doctor is interested in more information on this
subject, please contact us at
support@erdheim-chester.org for
information about how to contact the physician trying this approach.
·
Tamoxifen
Tamoxifen is a drug
used to treat some types of cancers. For more information on tamoxifen, see
http://en.wikipedia.org/wiki/Tamoxifen
).
·
Imatinib
Little has been published regarding this treatment.
However, one article has been found where this treatment was tried with 6
patients having multi-system involvement, who were not responding well to other
treatments. Two were stabilized and 4 continued to worsen on this treatment.
Most experienced stabilized cardiovascular involvement As more information is
known, this section will be updated (last update 6/26/09). Patients who are interested in
learning more about this as a possible treatment are encouraged to talk to their
doctors. For more information on Imatinib, see
http://en.wikipedia.org/wiki/Imatinib.
·
Long Term Antibiotics
Many ECD patients
report an increased tendency to suffer from infections and have a more difficult
time recovering from them. Some treatments can reduce a patient’s immune
system, putting them at a higher risk for infection. Most patients deal with
common infections such as sinus, upper respiratory, etc., but others may have to
deal with more opportunistic infections that occur when the immune system is
compromised. The following are various methods used by some doctors and
patients to help keep infections under control.
- Visit your local doctor as soon as you suspect an infection.
- Some doctors arrange a standing order for antibiotics in the event their
patient cannot see him/her in a timely manner. This is done on a case by case
basis. Even when using this method, it is very important to see your doctor as
soon as possible when you suspect an infection. Choosing the best antibiotic
for a particular infection can be very important and this can only be done with
proper testing. Many times an infection may be the result of a virus in which
case an antibiotic will NOT help in fighting the infection at all.
- Still other doctors place patients on long term courses of certain
antibiotics as a prophylactic treatment to prevent an infection. This is done
on a case by case basis and requires close monitoring by a doctor. There are
differing opinions on the benefits versus risks of this approach to treating
those with chronic infections.
For more information regarding antibiotics see
http://en.wikipedia.org/wiki/Antibiotic."
The efficacy of treatments is difficult to evaluate and the disease can be relentless in its course. In general, the clinical course of patients with this disease is variable. To find more information regarding these treatment options, the "Technical Papers" selection on this website provides journal articles regarding ECD, many of which provide anecdotal information about treatment options and results.
It is important to know there are patients who are living high quality lives with ECD for more than 18 years. Because ECD is so rare and publications so few, this information may not be readily available to patients or physicians.
Last updated: Dec 24, 2009