Clinical and Pathophysiological Investigations Into Erdheim Chester Disease
Condition: Myelofibrosis; Gaucher Disease; Pulmonary Fibrosis; Hermansky-Pudlak Syndrome (HPS); Cancer
MeSH terms: Pulmonary Fibrosis; Gaucher Disease; Hermanski-Pudlak Syndrome; Erdheim-Chester Disease
Study type: Observational

Summary: 
      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.
    

Detailed description: 
      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.
    

Observational model: Cohort
Time perspective: Prospective
Keywords: ECD; Erdheim-Chester Disease