Natural History of Diseases Associated With Allergic Inflammation: Atopic Dermatitis and Genetic and Congenital Diseases Associated With Atopic Pathways

Background:

Allergic inflammation is central to the pathogenesis of allergic diseases, including atopic
dermatitis, asthma, allergic rhinitis, and food allergy. These disorders are common,
affecting up to 50 million Americans, and their pathophysiology remains poorly understood.
Among allergic diseases, atopic dermatitis is common, with a prevalence of up to 20% in
children, is associated with the most dramatic elevations of IgE levels and most prominent
T-helper type 2 cell (Th2) inflammation, and treatment remains challenging. Atopic dermatitis
is also the first manifestation of allergic disease in many children, making it an ideal
disorder for studying the mechanisms of development and progression of allergic diseases. In
addition to atopic dermatitis, there are also a number of genetic and congenital diseases,
most presenting in childhood, that have prominent allergic manifestations, including
dermatitis, or affect atopic pathways. These disorders provide further opportunity for
advancing our understanding of the genetics and pathophysiology of diseases of allergic
inflammation. The NIAID Laboratory of Allergic Diseases (LAD) has a long interest in
exploring the mechanisms of allergic inflammation. Utilizing the resources of the LAD and the
NIH Clinical Center, we will advance our understanding of allergic inflammation and the
genetics and pathogenesis of allergic diseases through the study of these patients. The
findings of this protocol will have implications for improved diagnosis, treatment and
prevention of allergic diseases, including atopic asthma.

Objectives:

The overall goal of this exploratory protocol is to study the natural history of diseases of
allergic inflammation, focusing on subjects with moderate to severe atopic dermatitis or with
suspected genetic or congenital disorders associated with allergic inflammation. Research
studies obtained from participants will be used to explore the genetic, immunologic,
structural, and microbiologic abnormalities of these diseases. Research studies obtained from
blood samples, allergy skin testing, and skin biopsies of unaffective relatives and healthy
volunteers will be used as controls for assays and genetic tests. Results of research studies
will be correlated with clinical features of allergic manifestations of disease and response
to therapy.

Eligibility:

Subjects eligible for enrollment in this study include children and a subset of adults with
moderate to severe atopic dermatitis or children and adults with a suspected genetic or
congenital disorder associated with atopy or affecting an atopic pathway. Unaffected
relatives of an enrolled subject (both children and adults) and healthy adult volunteers will
also be eligible for separate enrollment.

Design:

The initial enrollment for this protocol will be 600 primary subjects over 5 years. In
addition, approximately 300 healthy or affected parents, siblings, or other relatives may be
enrolled for initial history and clinical and research laboratory evaluation only.
Approximately 150 unrelated healthy adult volunteers will be also enrolled. Atopic dermatitis
subjects in this study will receive standard care for allergic diseases, both outpatient and
inpatient, during the period of enrollment and will receive extensive evaluation as
clinically indicated, in addition to research studies.

- INCLUSION CRITERIA:

1. Subject or unaffected relatives must:

1. Be at least 2 years of age and less than or equal to 21 years of age at the
time of enrollment and have documented history of AD, by modified Hanifin
and Rajka criteria, that began in the first 5 years of life, that is
moderate to severe, and with continued active flares in the preceding 3
months. Patients greater than 21 years of age with active moderate to severe
AD may be enrolled, at the discretion of the PI or AIs, if they have a
history of AD in the first 5 years of life and/or, if in the opinion of the
PI or AIs, the patient would be of interest to fulfill the objectives of the
study.

OR

2. Be 2-80 years of age with a suspected genetic or congenital disorder
associated with atopy or affecting an atopic pathway, as determined by the
PI or AIs.

OR

3. Be an unaffected relative of a patient enrolled in the protocol.

2. Have a private physician to provide local continuity of care.

3. Provide a letter of referral, with copies of pertinent medical history and
laboratory studies as indicated, from prospective study participant s referring
physician; this is not a requirement for healthy relatives.

4. Be willing to donate blood, buccal swabs, saliva, skin and nasal swabs for
research and clinical studies and for storage to be used for future research; for
unaffected relatives, be willing to donate blood and/or undergo allergy skin
testing, in addition to having blood samples stored for future research.

Healthy Volunteer must:

1. Be at least 18 years old and no greater than 80 years old.

2. Have no history of recent, active, moderate to severe atopic dermatitis.

3. Be willing to have samples stored for research and genetic testing.

4. For a subset of subjects participating in the cooling cuff procedure, be willing to
have research skin biopsies performed.

EXCLUSION CRITERIA:

Any subject with any of the following criteria will be excluded:

1. Presence of conditions that, in the judgment of the investigator or the referring
physician, may put the subject at undue risk or make them unsuitable for participation
in the study.

2. Inability or refusal to undergo study procedures.

3. Inability to participate for the duration of the study.

Any unaffected relative or healthy volunteer with any of the following criteria will be
excluded:

1. Presence of conditions that, in the judgment of the investigator or the referring
physician, may put the subject at undue risk or make them unsuitable for participation
in the study.

2. Inability or refusal to undergo study procedures.