Anaphylaxis- what drives reactions severity?


Published Online: August 5, 2013

Prospective human studies of anaphylaxis and its mechanisms have been limited, with few severe cases and/or examining only one or two mediators. Therefore, we aimed to determine the clinical patterns of human anaphylaxis, including delayed deteriorations, risk factors, and the relationships between multiple immune mediators and reaction severity.

In a recent article published in The Journal of Allergy & Clinical Immunology (JACI), Brown et al studied cases of anaphylaxis presenting to eight Australian emergency departments over a three year period. Blood samples were taken to measure mast cell tryptase (MCT), histamine, anaphylatoxins (C3a, C4a, C5a), cytokines (interleukin (IL)-2, IL-6, IL-10, soluble tumor necrosis factor receptor I (TNFRI)), and platelet activating factor acetyl hydrolase (PAF-AH). These mediators, as well as baseline patient characteristics and reaction causation, were then studied to identify the risk factors and mediator patterns associated with reaction severity and delayed (recurrent, or "biphasic") deteriorations.

Severe anaphylaxis was found to be associated with older age, lung disease, and drug causation. These severe reactions presented as either hypotensive (low blood pressure), hypoxemic (low levels of oxygen in the blood), or a combination of both. All of the mediators that were measured were associated with severity, and one group (MCT, histamine, IL-6, IL-10 and TNFRI) was also associated with delayed deteriorations. These results suggest that multiple inflammatory pathways drive reaction severity. Low PAF-AH activity (the enzyme that degrades an important mediator, PAF) was also associated with severe reactions, confirming the findings of a previous study suggesting that patients with low levels of this enzyme are more susceptible to severe anaphylaxis. Delayed deteriorations requiring treatment with epinephrine occur in <10% of patients, and were associated with pre-existing lung disease and initially severe reactions. They probably represented a protracted inflammatory process intrinsically linked with initial reaction severity that may be masked by initial treatment with epinephrine. The study's findings supported current recommendations for safe observation periods after initial treatment.


The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.

AAAAI - American Academy of Allergy Asthma & Immunology