Abstract
Anaphylaxis in humans is inherently difficult to study due to the acuteness of symptoms and the lack of biomarkers serving as risk predictors. Most cases are related to IgE sensitizations to foods, insect venoms, and drugs with mastocytosis patients forming a smaller risk group. However, identifying the relatively small fraction of persons at risk has been exceedingly difficult. In this review, we propose to describe anaphylaxis in a broader context than defined by IgE sensitization alone. Exposure to a trigger, such as an allergen, may lead to anaphylaxis, but in particular, the internal dose sensed by the immune system needs to be established. Moreover, intrinsic patient factors as well as the specific circumstances of the exposure, i.e., the extrinsic factors, need to be thoroughly accounted for. More controversially, other triggers of anaphylaxis, such as increased sensitivity to or reduced catabolism of histamine (“histamine intolerance”) or mast cell activation syndrome also named mast cell activation disorder have been suggested, but still with very limited epidemiological evidence that a significant proportion of the observed reactions are caused by these alleged conditions. Thus, when all conditions are considered, it seems as if IgE-mediated reactions are responsible for the vast majority of anaphylactic conditions.
Highlights
Anaphylaxis is a serious allergic reaction that is rapid in onset and may cause death [1]
Tolerance”) or mast cell activation syndrome (MCAS) named mast cell activation disorder (MCAD) still have unclear definitions and limited epidemiological evidence exists that a significant proportion of anaphylaxis should be caused by these alleged conditions
We propose a theoretical framework for the pathogenesis of anaphylaxis, which by investigating a putative pathway of the mast cell activation, the primary target cells of the mast cell mediators, and of the neurological and other secondary mechanisms in the vasculature display a research paradigm that may help shedding some light on a disease, which by its acute form and unpredictable occurrence has so far eluded a more systematic study approach (Figure 1A)
Summary
Anaphylaxis is a serious allergic reaction that is rapid in onset and may cause death [1]. The hypersensitivity reaction classified by the British immuno logists, Philip Gell and Robin Coombs, as the type 1 reaction ( named the IgE-mediated allergic reaction, but notably IgE had still not been discovered and named in 1963, when Gell and Coombs first suggested their classification of this humoral form of hypersensitivity), still provides the basic theoretical framework for our discussion of anaphylaxis In this theory is the involvement of effector cell-bound antibodies, which upon binding to an allergen will induce activation and release of anaphylactogenic mediators. There is a large body of literature discussing the quality and quantity of IgE, in relation to anaphylaxis caused by foods, insect venoms, and drugs Many such studies suggest that not all allergens may necessarily be anaphylactogens, but since our aim is to go beyond this discussion, we will not dwell further on this aspect, but refer the reader to the vast amount of literature most recently reviewed in Ref. Many such studies suggest that not all allergens may necessarily be anaphylactogens, but since our aim is to go beyond this discussion, we will not dwell further on this aspect, but refer the reader to the vast amount of literature most recently reviewed in Ref. [6]
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