Approach to the Patient with Allergic or Immunologic Disease

Definition and Epidemiology

Diseases characterized by hypersensitivity of the immune system and inappropriate reactions to common environmental, food, and drug substances are termed allergic diseases. In the sensitized individual, common foods (e.g., peanut, milk, eggs), airborne particles (e.g., grass pollen, cat dander), drugs (e.g., aspirin, penicillin), insect stings (e.g., bees, wasps), or other agents (e.g., latex, dyes) can trigger an allergic reaction. Reactions can range from mild to severe to life-threatening, and symptoms can occur in one or many organs after skin contact, inhalation, ingestion of allergens, stings, or injections. The prevalence of allergic diseases has increased in recent decades. Although genetics plays a role in their etiology, potential explanations for the increase include improvements in hygiene, increased exposure to environmental pollutants, and alterations in diet and lifestyle. Climate change ( Chapter 17 ) also indirectly plays a role by increasing air pollutants (e.g., wildfires and sandstorms), altering the characteristics of pollens (concentrations, allergenic potential, and composition), and promoting the migration of species.

Allergic diseases can be classified based on the organs that are affected, the type of causal allergen, the interval between the exposure to the allergen and the onset of symptoms, and underlying mechanisms of the reaction. Allergic reactions may be immediate (minutes to 1 to 2 hours) or delayed (hours or days). Traditionally, hypersensitivity reactions have been classified into Type I, II, III, and IV ( Fig. 230-1 ). A more commonly used system classifies allergic reactions into immunoglobulin E (IgE)-mediated, mixed IgE- and cell-mediated, and non-IgE-mediated allergic diseases. IgE-mediated diseases are the best characterized allergic diseases, and reactions with high IgE levels are termed atopic diseases ( Table 230-1 ).

Pathobiology

Patients who have IgE-mediated allergic reactions undergo an initial sensitization phase during which IgE antibodies are produced to recognize a specific allergen and are bound to high-affinity FcɛRI receptors on mast cells or basophils. Further exposure to allergens can lead to cross-linkage of IgE antibodies with subsequent degranulation of mast cells or basophils. The initial sensitization phase occurs as epithelial cytokines interleukin-25 (IL-25), IL-33, and thymic stromal lymphopoietin are produced in response to the increased permeability of the allergen owing to a loss of integrity in the epithelial barrier. These cytokines enable differentiation of naïve T cells to T _h 2 cells as well as upregulation of cytokines (e.g., IL-4, IL-5, and IL-13) and IgE class-switching by B cells. Degranulation of mast cells and basophils leads to the release of histamine and other inflammatory mediators (e.g., cytokines, interleukins, leukotrienes, and prostaglandins) into the surrounding tissue, thereby causing several systemic effects, including vasodilation, the secretion of mucus, eosinophilic infiltration of tissues, and contraction of smooth muscle ( E-Fig. 230-1 ). Atopic sensitization is thought to occur via exposure to allergens through an impaired skin barrier, whereas tolerance is thought to be mediated through the gut. Loss of barrier integrity enables allergens to penetrate and to initiate an inflammatory immune cascade of events that leads to sensitization. The immune dysfunction then further exacerbates the impaired skin barrier to form a vicious cycle. Non-IgE-mediated reactions are poorly defined and are generally T-cell mediated.