Natural History of Severe Allergic Inflammation and Reactions

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. It 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, eosinophilic inflammation, and systemic immediate hypersensitivity reactions are heralding manifestation of allergic disease in many children, making these ideal disorders for studying the effector mechanisms promoting the development and progression of allergic diseases. In addition to these manifestations, there are also a number of characterized 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 individuals with severe allergic inflammation and hypersensitivity reactions, focusing on individuals and families with known or suspected inherited or acquired genetic causes for these clinical manifestations. Research studies obtained from blood, skin, saliva, bone marrow, and other tests 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 unaffected 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 a known or suspected inherited or acquired genetic allergic disorder leading to severe allergic inflammation or reactions. 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. 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 also be enrolled. Affected 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.