Chapter 190

A precipitous increase in incidence and prevalence of allergic diseases in the last decades leads to the current estimate that up to 50% of the population of Western societies shows reactivity on skin testing to one or more environmental allergens.1 In some subpopulations, up to one in four children suffer from asthma. One explanation for this dramatic increase in allergic diseases is the “hygiene hypothesis,” which posits that a decrease in the exposure to microbes due to improved hygiene, smaller families, less breastfeeding, more immunizations, and lack of serious childhood infections results in altered immunoregulation and deviation toward an allergic disease-promoting TH2 response. Microbial exposure promotes the production of regulatory T cells involved in maintaining tolerance to allergens (see Chapter 186). Lack of sufficient microbial exposure may result in weakened tolerance and, in the setting of other factors such as genetic predisposition and environmental exposures, result in the promotion of allergic diseases.

Allergic diseases are immunological diseases in that their genesis and manifestations result from the functioning of components of the immune system. Disease pathogenesis is mediated by both innate immune responses, involving mast cells, basophils, eosinophils, and dendritic and Langerhans cells, as well as acquired immune responses involving T and B lymphocytes. Orchestrating the allergic response is the TH2 CD4+ T-helper-cell lineage, which is now appreciated to play a central role in the pathogenesis of allergic diseases. TH2 cells recruit other components of the innate and acquired immune response by virtue of their production of a set of proatopic cytokines, including IL-4, IL-5, IL-10, and IL-13.2 They promote the production of IgE, a key trigger of immediate hypersensitivity reactions, and help sustain chronic allergic inflammation in such diseases as asthma and eczema.

The increased knowledge of allergic diseases and their pathogenesis has stimulated the development of new therapeutic approaches, including desensitization therapy with defined allergen preparations or pharmacologic interventions aimed at depleting IgE or targeting the action of mediators such as leukotrienes.

Allergic disorders develop when individuals with a genetic predisposition are exposed to environmental triggers.3 A unifying attribute of these disorders is atopy, defined as a genetically determined predisposition (and hence tends to be familial) to generate IgE antibodies on exposure to environmental antigens. Subsequent exposure to the offending antigen, or allergen, triggers an immediate hypersensitivity reaction. This is an IgE-mediated tissue response that is characterized by increased vascular permeability, vasodilatation, smooth muscle contraction, and local inflammation. The atopic (or allergic) trait integrates pathways of the acquired immune response, including specialized T helper cells and IgE-producing B cells, as well as components of the innate immune response, including mast cells, eosinophils, basophils, and neutrophils. These pathways are critical to pathogenesis in allergic diseases. In contrast, many adverse reactions to foods or drugs are not allergic in nature in that they proceed independently of the immune system, for example, milk intolerance from lactase. Some immune-mediated reactions are not allergic because they ...

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