In localized anaphylaxis, the reaction is limited to a specific target tissue or organ, often involving epithelial surfaces at the site of allergen entry. The tendency to manifest localized anaphylactic reactions is inherited and is called atopy. Atopic allergies, which afflict at least 20% of the population in developed countries, include a wide range of IgE-mediated disorders, including allergic rhinitis (hay fever), asthma, atopic dermatitis (eczema), and food allergies.
ALLERGIC RHINITIS The most common atopic disorder, affecting 10% of the U.S. population, is allergic rhinitis, commonly known as hay fever. This results from the reaction of airborne allergens with sensitized mast cells in the conjuncti-vae and nasal mucosa to induce the release of pharmacologically active mediators from mast cells; these mediators then cause localized vasodilation and increased capillary permeability. The symptoms include watery exudation of the con-junctivae, nasal mucosa, and upper respiratory tract, as well as sneezing and coughing.
ASTHMA Another common manifestation of localized ana-phylaxis is asthma. In some cases, airborne or blood-borne allergens, such as pollens, dust, fumes, insect products, or viral antigens, trigger an asthmatic attack (allergic asthma); in other cases, an asthmatic attack can be induced by exercise or cold, apparently independently of allergen stimulation (intrinsic asthma). Like hay fever, asthma is triggered by degranulation of mast cells with release of mediators, but instead of occurring in the nasal mucosa, the reaction develops in the lower respiratory tract. The resulting contraction of the bronchial smooth muscles leads to bronchoconstric-tion. Airway edema, mucus secretion, and inflammation contribute to the bronchial constriction and to airway obstruction. Asthmatic patients may have abnormal levels of receptors for neuropeptides. For example, asthmatic patients have been reported to have increased expression of receptors for substance P, a peptide that contracts smooth muscles, and decreased expression of receptors for vasoactive intestinal peptide, which relaxes smooth muscles.
Most clinicians view asthma as primarily an inflammatory disease. The asthmatic response can be divided into early and late responses (Figure 16-8). The early response occurs within minutes of allergen exposure and primarily involves hista-mine, leukotrienes (LTC4), and prostaglandin (PGD2). The effects of these mediators lead to bronchoconstriction, vaso-dilation, and some buildup of mucus. The late response occurs hours later and involves additional mediators, including IL-4, IL-5, IL-16, TNF-a, eosinophil chemotactic factor (ECF), and platelet-activating factor (PAF). The overall effects of these mediators is to increase endothelial cell adhesion as well as to recruit inflammatory cells, including eosinophils and neutrophils, into the bronchial tissue.
The neutrophils and eosinophils are capable of causing significant tissue injury by releasing toxic enzymes, oxygen radicals, and cytokines. These events lead to occlusion of the bronchial lumen with mucus, proteins, and cellular debris; sloughing of the epithelium; thickening of the basement membrane; fluid buildup (edema); and hypertrophy of the bronchial smooth muscles. A mucus plug often forms and adheres to the bronchial wall. The mucus plug contains clusters of detached epithelial-cell fragments, eosinophils, some neutrophils, and spirals of bronchial tissue known as Cursch-mann's spirals. Asthma is increasing in prevalence in the United States, particularly among children in inner-city environments (see Clinical Focus on page 376).
FOOD ALLERGIES Various foods also can induce localized anaphylaxis in allergic individuals. Allergen crosslinking of IgE on mast cells along the upper or lower gastrointestinal tract can induce localized smooth-muscle contraction and vasodilation and thus such symptoms as vomiting or diarrhea. Mast-cell degranulation along the gut can increase the permeability of mucous membranes, so that the allergen enters the bloodstream. Various symptoms can ensue, depending on where the allergen is deposited. For example, some individuals develop asthmatic attacks after ingesting certain foods. Others develop atopic urticaria, commonly known as hives, when a food allergen is carried to sensitized mast cells in the skin, causing swollen (edematous) red (ery-thematous) eruptions; this is the wheal and flare response, or P-K reaction, mentioned earlier.
ATOPIC DERMATITIS Atopic dermatitis (allergic eczema) is an inflammatory disease of skin that is frequently associated with a family history of atopy. The disease is observed most frequently in young children, often developing during infancy. Serum IgE levels are often elevated. The allergic individual develops skin eruptions that are erythematous and filled with pus. Unlike a delayed-type hypersensitive reaction, which involves TH1 cells, the skin lesions in atopic dermatitis have TH2 cells and an increased number of eosinophils.
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