Update on refractory anaphylaxis.

PURPOSE OF REVIEW: The rising incidence of anaphylaxis and reports of cases unresponsive to standard epinephrine treatment highlight the relevance of refractory anaphylaxis. There is a lack of standardized management protocols, and clinicians across specialties need guidance to handle this rare but life-threatening condition.

RECENT FINDINGS: There is a lack of a universally accepted definition, with most studies describing it as anaphylaxis unresponsive to several doses of intramuscular epinephrine. It emphasizes the pathophysiological complexity, including potential mechanisms like delayed epinephrine absorption, atypical mediator release, or underlying comorbidities. Management relies on recommendations ranging from intravenous epinephrine to adjunctive treatments. We call attention to gaps in clinical guidelines and research, advocating for more data on incidence, risk factors, and effective interventions, especially in emergency settings.

SUMMARY: There is a need for clear protocols to help recognize and manage cases of refractory anaphylaxis. This includes awareness of when to escalate care, use intravenous epinephrine or adjunctive agents. For research, the variability in definitions and treatment approaches points to the need for standardized diagnostic criteria and prospective studies to better understand risk factors, outcomes, and optimal management strategies. Additionally, there is a strong case for exploring biomarkers and therapies that may improve early identification and treatment of high-risk cases.