This study will investigate how, why and under what conditions eosinophils (a type of white
blood cell) become activated and will examine their function in immune reactions. Eosinophil
counts often rise in response to allergies, asthma, and parasitic worm infections. They can
also go up in uncommon autoimmune conditions and, rarely, in association with tumors.
Elevated levels of these cells is called eosinophilia. Usually, eosinophilia causes no
apparent symptoms, but in rare cases there may be local swelling and itching, allergic lung
problems, heart disease or nerve damage caused by the release of toxic substances in these
cells into body tissues.
Patients 1 to 100 years of age with eosinophil counts greater than 750/ml or an abnormal
accumulation of eosinophils in the skin or body tissues may be eligible for this study. All
participants will have a thorough medical history, physical examination and blood tests.
Depending on the person's age and symptoms, other diagnostic tests may be done, including
specialized studies of the eye, lungs, skin, bone marrow, nerves or heart. This is not a
treatment study, and no experimental treatments will be offered. Patients who require
treatment will receive standard medical care.
Certain other procedures may be requested solely for research purposes. All participants will
be asked to donate extra blood for laboratory studies investigating how immune cells and
other immune substances in the blood act to stimulate a rise in eosinophils. In addition,
some participants may undergo one or more of the following:
- <TAB>Annual Follow-up evaluations - Physical examinations and blood tests to evaluate
changes in the patient's condition and eosinophil counts over time.
- <TAB>Bone marrow biopsy and aspiration will be recommended during the initial
evaluation, and in certain patients at other times when it is important to look directly
at the newly developing cells in the bone marrow. For this procedure an area of skin and
bone is anesthetized with xylocaine (an anesthetic similar to that used by dentists),
and a very sharp needle is used to sample the bone marrow for evaluation. Bone marrow
biopsy and aspiration can have side effects of pain and/or bleeding into the skin and
soft tissues at the site of the procedure. Rarely the area at the biopsy site can become
infected, and is treated with antibiotics.
- <TAB>Genetic testing: Some of the blood drawn from you as part of this study will be
used for genetic tests. Genetic tests can help researchers study how health or illness
is passed on to you by your parents or from you to your children. Any genetic
information collected or discovered about you or your family will be confidential.
- <TAB>Leukapheresis (only patients 18 years and older) to collect large numbers of
certain cells - In this procedure, whole blood is collected through a needle placed in
an arm vein. The blood circulates through a machine that separates it into its
components. The white cells are then removed and the rest of the blood is returned to
the body, either through the same needle used to draw the blood or through a second
needle placed in the other arm....
Subjects admitted on this protocol will have elevated eosinophil counts in the peripheral
blood or tissues or will be relatives of subjects with eosinophilia. Eosinophilic subjects
will undergo an extensive clinical evaluation focused on the identification of the cause of
eosinophilia and the presence of end organ manifestations. In addition, they will be
characterized in detail immunologically, and their blood cells and/or serum will be collected
to provide reagents (eg. specific antibodies, T-cell clones, etc.) that will be used in the
laboratory to address broader questions relating to the etiology of eosinophilia, its
immunoregulation, the degree and source of eosinophil activation, and/or the functional role
of eosinophils in the afferent arm of those immune response where they are prominent. While
the protocol is not primarily designed to study treatment of patients with blood and tissue
eosinophilia, the clinical and immunological responses to various medically indicated
therapies will be carefully monitored. The subjects themselves will be followed over time to
determine the kinetics and nature of the factors affecting their degree of eosinophilia and
the level of activation or degranulation of the eosinophils at various time points and in
response to various stimuli. It is anticipated that the subjects will receive a degree of
clinical evaluation, care and monitoring more extensive than that generally available and
that the specimens collected from them will prove to be valuable reagents for laboratory
studies related to eosinophilia, eosinophil activation and function. Recognized causes of
subjects hypereosinophilia will be treated appropriately either by our own clinical service
or by the referring physicians. Standard of care therapy may be provided when indicated for
HES variants. This protocol will also allow clinical and laboratory evaluation of family
members of subjects with eosinophilia in order to help identify genetic causes of
eosinophilia and to provide controls for immunologic studies. Interviews will be conducted on
a subset of HES patients to provide information about patient signs and symptoms for use in
the development of a patient-related outcomes questionnaire for use in future treatment
studies. Finally, adult subjects with gastrointestinal involvement may be asked to provide
stool samples for microbiome analysis and assessment of stool levels of eosinophil granule
proteins to explore the role of the microbiome in eosinophilic gastrointestinal disease.
Stool samples may also be obtained from adult subjects undergoing endoscopy and/or
colonoscopy as part of their initial evaluation and/or assessment of response to treatment.
Potential confounding variables, including body mass index, diet, stool transit time and
vitamin D levels will be assessed at the time of stool collection.
- ELIGIBILITY CRITERIA (EOSINOPHILIC SUBJECTS):
1. 1-100 years of age
2. documented peripheral blood eosinophil count >1500/mm3, tissue eosinophilia (abnormal
accumulation of eosinophils in the skin or other body tissues) or suspected
eosinophilic end organ involvement
3. has a primary (non-NIH) physician for routine medical care
1) medical conditions or therapies that the investigator feels put the subject at
unacceptable risk for participation in the study
ELIGIBILITY CRITERIA (RELATIVES):
1. 1-100 years of age
2. extended family member of a study participant in 94-I-0079
1) any condition that the investigator feels put the subject at unacceptable risk for
participation in the study.