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

Summary

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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 disea...

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 1500 primary subjects over 5 years. In addition, approximately 500 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.

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