IgE antibodies occupy receptor sites on mast cells. Within minutes after exposure to the allergen, a multivalent antigen links adjacent IgE molecules, activating and degranulating mast cells. Clinical manifestations can be explained by the effects of released mediators on target end organs. Both preformed and newly generated mediators cause vasodilation and permeability changes, visceral smooth muscle contraction, mucous secretory gland stimulation, vascular permeability, and tissue inflammation. Arachidonic acid metabolites, cytokines, and other mediators (such as chemoattractants) induce a late-phase inflammatory response that appears several hours later in affected tissues when antigen exposure is continuous (eg, pollen) or chronic.
Anaphylaxis is the most serious and potentially life-threatening manifestation of mast cell and basophil mediator release. Anaphylaxis is defined clinically under the following circumstances: (1) an allergen exposure followed by the acute onset of illness involving skin or mucosal tissue and either respiratory compromise or hypotension (systolic blood pressure less than 90 mm Hg or 30% less than known baseline); (2) a likely allergen exposure followed by the acute onset of two or more of the following conditions: skin or mucosal tissue involvement, respiratory compromise, hypotension, and persistent gastrointestinal symptoms; or (3) a known allergen exposure followed by hypotension.
IgE-dependent anaphylaxis is usually an acute syndrome initiated by a new allergen exposure after a prior silent exposure has sensitized the patient with IgE antibodies. Thus, anaphylaxis (or systemic allergic reactions which do not meet the definition of anaphylaxis) cannot occur on first-time exposure to allergens like drugs, insect venoms, latex, and foods. In contrast, other syndromes of anaphylaxis (sometimes called “anaphylactoid”), such as reactions to radiocontrast media and most NSAID and opioid reactions, are pseudoallergic without known immunologic mechanisms and can occur with first-time exposure.
Symptoms and signs typically occur within 30 minutes of initial exposure but may appear up to several hours later. These include (in order of frequency) (1) skin manifestations, typically urticaria but also flushing, blotchy rashes, and pruritus; (2) respiratory distress, including wheezing, stridor, bronchospasm, and airway angioedema; (3) gastrointestinal symptoms, including cramping, emesis, and diarrhea (especially in food allergy); and (4) hypotension, often manifested as lightheadedness, dizziness, or syncope. The condition is potentially fatal, especially if untreated, and can affect both nonatopic and atopic persons.
Identification of anaphylaxis is clinical as the need for treatment is urgent. Elevated serum levels of mast cell mediators, such as tryptase and histamine, may be detected shortly after a reaction providing support to the diagnosis. Referral to an allergy specialist is standard because of concern for a future reaction and need for appropriate interventions and education. Specific IgE serum or skin testing may be performed to suspected allergens. Skin testing, which is usually more sensitive, optimally occurs 4–6 weeks after a severe reaction ...