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
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 ...