Clinical and Pathophysiological Investigations Into Erdheim Chester Disease
Clinical and Pathophysiological Investigations Into Erdheim Chester Disease
Background:

 - Erdheim Chester Disease (ECD) is a very rare disease in which abnormal white blood cells
 start growing and affect the bones, kidneys, skin, and brain. ECD can cause severe lung
 disease, kidney failure, heart disease, and other complications that lead to death. Because
 ECD is a rare disease, found mostly in men over 40 years of age, there is no standard
 treatment for it. More information is needed to find out what genes can cause ECD and how
 best to treat it.

 Objectives:

 - To collect study samples and medical information on people with Erdheim Chester Disease.

 Eligibility:

 - Individuals 2 to 80 year of age who have been diagnosed with Erdheim Chester Disease.

 Design:

 -  Participants will be screened with a physical exam and medical history.

 -  Participants will have a study visit to provide samples for study, including blood,
 urine, and skin tissue samples. Participants will also have lung, heart, and muscle
 function tests; imaging studies of the brain, chest, and whole body; a treadmill running
 stress test; an eye exam; and other tests as needed by the study doctors.

 -  Participants will be asked to return for a similar set of tests every 2 years, and to
 remain in contact for possible treatment options.
Rare and potentially lethal, Erdheim-Chester Disease (ECD) is a histiocytic neoplasm about
 which little is known, and for which there remains a paucity of effective treatments.
 Histologically, it is categorized as a non-Langerhans cell histiocytosis, and most commonly
 occurs in men between the ages of 50 and 70, although cases have been reported in women, and
 rarely, children. Worldwide about 600 cases have been reported, and the disorder remains
 difficult to diagnose due to its rarity and protean manifestations. The phenotype of ECD
 ranges from almost asymptomatic patients diagnosed incidentally when imaging studies are done
 for other reasons, to patients presenting with multiple organ failure who die shortly after
 diagnosis. These multifarious presentations, and the subsequent response to therapy, have not
 been well documented and create the need for a prospective study to learn more about this
 devastating disorder.

 Protocol 11-HG-0207, "Clinical and Pathophysiological Investigations into Erdheim-Chester
 Disease," is a natural history study designed to better understand and describe the natural
 history, pathophysiology, and response to therapy, of this devastating disorder. We will use
 a prospective design to enroll and follow qualified men and women, of all ethnic groups, ages
 2 to 80 years, who will be screened for candidacy prior to enrollment. If appropriate for the
 study, patients may opt to be evaluated at the NIH Clinical Center, or may opt to send tissue
 and records for analysis. The NIH Clinical Center will be the only center for this study, and
 patients may return for follow-up visits every two to three years, or send copies of test
 results in lieu of an admission. The enrollment ceiling is 100 patients and we may close the
 study to new recruitment at that time, but keep the study open to see established patients
 and to analyze data. Thus, we do not have a definite time-period for the completion of the
 study.

 Through the prospective design, we will collect data from medical histories and physical
 exams, lab tests, imaging studies, organ-function studies, various measurement tools, and
 medical consultations. Data will be collated into spreadsheets and divided into functional
 categories such as organ system complications, to facilitate analysis. We will analyze the
 data with the assistance of an NIH statistician using parametric and non-parametric methods
 to assess overall trends in survival, and to look for patterns in organ involvement, patterns
 in response to various therapeutic regimens, and, lastly, to look for an association between
 the BRAF V600E mutation and disease severity.

 Patient safety and privacy, and respect for the autonomy of the patients, are our top
 priorities. All patients will be carefully screened prior to participation, and we follow
 Clinical Center policies regarding informed consent. Data will be stored electronically and
 in hard copy, in password protected computers and locked cabinets, respectively. Only the PI,
 the responsible physician, and select AIs, will have access. Patients will be closely
 monitored during NIH admissions, and the investigators will track all adverse events
 according to NIH policy. The investigators will keep patients apprised of test results and
 will reiterate the risks and benefits of procedures during NIH evaluations. Lastly, the
 investigators will respect patients rights to refuse testing.

 We will disseminate the results of our analyses in publications and presentations intended to
 educate the medical community regarding the diagnosis and management of ECD, and to spur
 research. We hope our efforts will eventually lead to better outcomes for patients.
-  INCLUSION CRITERIA:

 -  ECD patients of any gender and ethnicity age 2-80 years are eligible to enroll in this
 protocol.

 -  Patients will be diagnosed as having ECD based upon pathologic evaluations of affected
 organs.

 -  Any child older than 2 years with confirmed ECD by pathology will be enrolled in our
 study since childhood cases are so rare. The child must be clinically stable prior to
 visiting the NIHCC.

 -  Patients that agree to be part of this research study are expected to undergo the
 evaluations and testing of this protocol.

 EXCLUSION CRITERIA:

 -  Patients will be excluded if they have a suspected diagnosis of ECD not confirmed by
 biopsy or another form of histiocytosis.

 --If the patients cannot travel to the NIH because of their medical condition, they
 can still participate in our study by submitting tissue and blood for research
 purposes after consent has been obtained and diagnosis of ECD has been confirmed
 through tissue-biopsy evaluation. This exception applies to all patients aged 2-80
 years.

 -  Children under age two years are excluded because there is no urgency for a very early
 diagnosis and care is more readily provided to older children at the Clinical Center.

 -  Pregnant women will not take part in this study because of the fetal risks, unless
 they will be participating by only submitting samples of previously collected tissue.
 We will not encourage pregnant women to undergo affected organ surgery or biopsy to
 participate in this study, unless clinically indicated and recommended by their
 private physicians.