Refractory Anaphylaxis: A New Entity for Severe Anaphylaxis

Anaphylaxis reactions lie on a spectrum of severity, ranging from relatively mild lower respiratory involvement (depending on the definition of anaphylaxis used) to more severe reactions that are refractory to initial treatment with epinephrine and may rarely cause death. A variety of grading scales exist to characterize severe reactions, but there is a lack of consensus about the optimal approach to define severity. More recently, a new entity called refractory anaphylaxis (RA) has emerged in the literature, characterized by the persistence of anaphylaxis despite initial epinephrine treatment. However, slightly different definitions have been proposed to date. In this Rostrum, we review these definitions as well as data relating to epidemiology, elicitors, risk factors, and management of RA. We propose a need to align the different definitions for RA, to improve epidemiological surveillance, advance our understanding of the pathophysiology of RA, and optimize management strategies to reduce morbidity and mortality.