Introduction
Anaphylaxis is a serious systemic hypersensitivity reaction that is usually rapid in onset and may cause death in its more severe form (1). Therefore, it requires fast and appropriate medical management (1). Individual risk factors and cofactors that affect the severity of anaphylaxis have been described (2, 3).
In the classical form, anaphylaxis is triggered by mediators released by activated mast cells after cross-binding of surface-bound immunoglobulin E (IgE) by an allergen, but it can also be activated by other immunologic and non-immunologic elicitors. This activation leads to a release of mast cell tryptase in the blood, which can be measured and used as a diagnostic tool.
Low levels of tryptase are secreted permanently even in the absence of mast cell activation and reflect total body mast cell burden. Therefore, baseline tryptase levels are elevated in systemic mastocytosis (4) but also slightly increased in older people and in males versus females (5, 6, 7). A high baseline tryptase level is known to be associated with severe anaphylaxis (8, 9, 10, 11).
The acute phase of anaphylaxis typically occurs within minutes after contact with the allergen and then symptoms regress within 4 hr (12). However, anaphylaxis can also be biphasic, which means that after initial symptoms completely resolve, a new onset of symptoms occurs without re-exposure to an elicitor (13). The reported incidence of biphasic anaphylaxis ranges from 0.4% to 23.3%, but more recent data indicate 4% to 5% (14, 15, 16, 17, 18). The mechanism in biphasic anaphylaxis in humans is known to be a prolonged expression of the initial IgE-mediated reaction rather than an additional mechanism (19, 20).
A biphasic reaction usually occurs at 1 to 48 hr after the initial reaction (14, 17, 21, 22) and in rare instances up to 72 hr (23, 24). Symptoms of this second-phase reaction can be less than, as much as, or more severe than the first reaction. (25). Biphasic hypersensitivity reactions are globally more severe than are monophasic reactions (26). Therefore, close monitoring is recommended for 1 to 6 hr after an anaphylactic reaction, depending on the clinical severity, and potentially up to 12 hr in some cases (27, 28). A previous history of anaphylaxis (26), severe anaphylaxis (29), greater number of doses of adrenaline during medical care (30), delay in initiation of medical care or administration of epinephrine (17, 31), cardiovascular disease (32), history of drug anaphylaxis (33, 34), an unknown elicitor (14, 26), an oral allergen elicitor (35) and age 6 to 9 years (36) have been described as risk factors for a biphasic reaction.
Here we analysed the clinical parameters of biphasic reactions. Because the occurrence of a biphasic reaction has been associated with the severity of anaphylaxis (26, 37, 38, 39) and elevated basal tryptase is associated with anaphylaxis severity (40, 41, 42), we also compared plasma tryptase levels in patients with monophasic and biphasic reactions.