Anaphylaxis

Abstract

Anaphylaxis occurs commonly in community settings. The rate of occurrence is increasing, especially in young people. Understanding potential triggers, mechanisms, and patient-specific risk factors for severity and fatality is the key to performing appropriate risk assessment in those who have previously experienced an acute anaphylactic episode. The diagnosis of anaphylaxis is based primarily on clinical criteria and is valid even if the results of laboratory tests, such as serum total tryptase levels, are within normal limits. Positive skin test results or increased serum specific IgE levels to potential triggering allergens confirm sensitization but do not confirm the diagnosis of anaphylaxis because asymptomatic sensitization is common in the general population. Important patient-related risk factors for severity and fatality include age, concomitant diseases, and concurrent medications, as well as other less well-defined factors, such as defects in mediator degradation pathways, fever, acute infection, menses, emotional stress, and disruption of routine. Prevention of anaphylaxis depends primarily on optimal management of patient-related risk factors, strict avoidance of confirmed relevant allergen or other triggers, and, where indicated, immunomodulation (eg, subcutaneous venom immunotherapy to prevent Hymenoptera sting-triggered anaphylaxis, an underused, potentially curative treatment). The benefits and risks of immunomodulation to prevent food-triggered anaphylaxis are still being defined. Epinephrine (adrenaline) is the medication of first choice in the treatment of anaphylaxis. All patients at risk for recurrence in the community should be equipped with 1 or more epinephrine autoinjectors; a written, personalized anaphylaxis emergency action plan; and up-to-date medical identification. Improvements in the design of epinephrine autoinjectors will help to optimize ease of use and safety. Randomized controlled trials of pharmacologic agents, such as antihistamines and glucocorticoids, are needed to strengthen the evidence base for treatment of acute anaphylactic episodes.

Identification of markers that distinguish IgE- from IgG-mediated anaphylaxis

“…Currently, increases in serum tryptase levels are the preferred assay for detection of mast cell-mediated anaphylaxis in humans (1,10). To determine whether a similar increase in a mast cell-specific protease could differentiate IgE-from IgG-mediated anaphylaxis in mice, we determined serum MMCP1 levels before and after IgE-and IgGmediated anaphylaxis in this species.…”

“…rodent | histamine | platelet activating factor | mast cell A naphylaxis (immune-mediated shock) results from rapid release of large quantities of vasoactive mediators that increase vascular permeability, cause smooth muscle contraction, and decrease cardiac output (1,2). In mice, two pathways that lead to anaphylaxis have been defined: the classic pathway, which is mediated by IgE, Fcε receptor I (FcεRI), mast cells, and histamine > platelet activating factor (PAF); and the alternative pathway, which is mediated by IgG, Fcγ receptor III (FcγRIII), and macrophage and basophil secretion of PAF (3)(4)(5).…”

“…In humans, the IgE pathway of anaphylaxis has been well characterized, whereas the existence of an IgG pathway is controversial (1,(7)(8)(9). Although increased serum levels of tryptase, which is released by degranulating mast cells, suggests IgE-mediated anaphylaxis (10)(11)(12), many cases of human anaphylaxis are not accompanied by elevated serum tryptase or detectable antigen-specific IgE (2, 7).…”

Oral antihistamines: concise guide to properties and current use

“…2 Adrenaline is the most important drug in the management of anaphylaxis. 2,3 Delayed administration of adrenaline is associated with significantly worse clinical outcomes and death.…”

“…1 Although GP prescribing of all formulations of oral antihistamines has been increasing in recent years (by 7 per cent in the two years to 2008), costs have fallen substantially (by 40 per cent since 2000 and 14 per cent since 2006). 2 In primary care in England, cetirizine is the most frequently prescribed antihistamine (36 per cent of total volume), followed by loratadine (19 per cent). However, these agents together account for only 22 per cent of costs; desloratadine and fexofenadine, though less frequently prescribed (8 and 14 per cent of volume respectively), account for 21 and 31 per cent of spending.…”