Definition

In some cases, the immune response to antigen is greatly exaggerated, a situation referred to as hypersensitivity. Anaphylaxis is a life-threatening response that a sensitized person develops within minutes after administration of a specific antigen. Hypersensitivity reactions are classified as types I, II, III, and IV.

Type I hypersensitivity pathophysiology

Type I hypersensitivity is a rapidly developing reaction that results from antigen–antibody interaction in an individual who has been previously exposed and sensitized to the antigen. The responsible antigen, referred to as an allergen, reacts with specific IgE antibodies on tissue mast cells and circulating basophils to trigger mediator release and an allergic response. A key mediator of allergic symptoms is histamine, which is described in the following section. Chemically, allergens are usually proteins, and a multitude of environmental factors, including grass, pollen, dust, mites, molds, and animal dander, can generate type I hypersensitivity reactions.

Clinical manifestations

Allergic reactions present with symptoms such as rhinitis, conjunctivitis, urticaria, pruritus, and possibly anaphylaxis. The term anaphylaxis refers to a severe, generalized, immediate hypersensitivity reaction that includes pruritus, urticaria, angioedema (especially laryngeal edema), hypotension, wheezing and bronchospasm, and direct cardiac effects (including arrhythmias). A shocklike state can develop from hypotension secondary to systemic vasodilatation and extravasation of protein and fluid. Clinical manifestations of an allergic reaction can occur in various combinations and usually occur within minutes of exposure to the precipitating antigen(s). In some cases, though, the onset of signs and symptoms may be delayed for 1 hour or longer. Signs and symptoms can be protracted and variably responsive to treatment. Biphasic anaphylaxis can also occur, in which early signs and symptoms clear, either spontaneously or after acute therapy, and symptoms reoccur several or many hours later. Generally, the severity of an anaphylactic event relates to the suddenness of its onset and to the magnitude of the challenge (i.e., the greater the provocative stimulus, the more severe is the reaction). However, anaphylaxis can occur after exposure to minute amounts of allergen in highly sensitive individuals.

Anaphylactoid reactions are caused by mediator release from basophils (but not from mast cells) in response to a non–immunoglobulin E (IgE)-mediated triggering event. Such reactions present with similar clinical manifestations as those with anaphylaxis; however, it has been reported that cutaneous symptoms are more frequent and cardiovascular collapse is less frequent in patients experiencing anaphylactoid reactions versus those experiencing anaphylactic reactions.

Tryptase is a marker for mechanistic delineation of an allergic response. It is an enzyme that is released from mast cells along with histamine and other inflammatory mediators during an allergic response. A significantly elevated tryptase level (>25 mcg/L) strongly suggests an allergic mechanism. The presence of a normal tryptase level, however, does not exclude an immunologic reaction because elevated tryptase levels are not found in almost one-third of anaphylactic cases. Although the diagnosis of anaphylaxis should not rely on a single test, the high positive predictive value of tryptase makes it useful medicolegally and for subsequent patient management.