Identifying and managing those at risk for vaccine related allergy and anaphylaxis

Immediate hypersensitivity reactions to vaccines, the most severe of which is anaphylaxis, are uncommon events occurring in less than 1 in a million doses administered. These reactions are infrequently IgE-mediated. Since they are unlikely to recur, a reaction to a single dose of a vaccine is rarely a contraindication to redosing. This narrative review article contextualizes the recent knowledge we have gained from the COVID-19 pandemic rollout of the new mRNA platform with the SARS-CoV-2 vaccines within the much broader context of what is known about immediate reactions to other vaccinations of routine and global importance. We focus on what is known about evidence-based approaches to diagnosis and management and what is new in our understanding of mechanisms of immediate vaccine reactions. Specifically we will review the epidemiology of immediate hypersensitivity vaccine reactions, differential diagnosis for immune-mediated and non-immune reaction clinical phenotypes, including how to recognize immunization stress related responses. In addition, we will highlight what is known about mechanisms and will review the rare but important contribution of excipient allergies and specifically when to consider testing for them as well as other key features that contribute to safe evaluation and management.