Purpose of review: In the century since the discovery of anaphylaxis, research has yet to identify the mechanisms that cause a localized allergic response to become rapidly generalized, and particularly why only some sensitized individuals develop the clinical reaction on exposure. The possible components and steps in the process (proven and hypothetical) are reviewed with respect to their variation and regulation and their potential for therapeutic intervention.
Recent findings: Studies of insect sting allergy have revealed some of the gaps in our understanding, the relatively poor predictive value of our diagnostic tests, and more recently the early evidence for 'priming' of basophils and mast cells as a precursor or predictor of clinical reactivity. Recent literature has elucidated some of the products and regulatory pathways of the cells involved in the initiation of the anaphylactic response, the role of neurologic pathways, and the possible 'on-off switches' at the level of the immunoglobulin E receptors and their related signaling pathways.
Summary: This review incorporates old and new observations that may be related to the puzzling characteristics of anaphylaxis. Recognizing the gaps in our understanding helps to identify many areas that require further study and presents promising targets for future treatment and prevention of anaphylaxis.