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Update on refractory anaphylaxis.

Paula Galvan-Blasco1,2, Javier Pereira-Gonzalez1,2, Victoria Cardona1,2

  • 1Department of Allergology, Hospital Universitari Vall d'Hebron.

Current Opinion in Allergy and Clinical Immunology
|August 1, 2025
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Summary
This summary is machine-generated.

Refractory anaphylaxis, unresponsive to standard treatment, requires clearer management guidelines. Research is needed for standardized definitions, risk factors, and optimal interventions for this severe allergic reaction.

Keywords:
adrenalinedistributive shockepinephrinerefractory anaphylaxissevere anaphylaxis

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Area of Science:

  • Allergy and Immunology
  • Emergency Medicine

Background:

  • Anaphylaxis incidence is rising, with increasing reports of cases refractory to standard epinephrine treatment.
  • Refractory anaphylaxis poses a significant clinical challenge due to a lack of standardized management protocols.

Purpose of the Study:

  • To review current understanding and management of refractory anaphylaxis.
  • To highlight the need for improved clinical guidance and research in this area.

Main Methods:

  • Literature review focusing on refractory anaphylaxis definitions, pathophysiology, and management strategies.
  • Analysis of existing clinical recommendations and identification of research gaps.

Main Results:

  • A universally accepted definition for refractory anaphylaxis is lacking; it's often described as unresponsiveness to multiple intramuscular epinephrine doses.
  • Pathophysiological complexity includes delayed absorption, atypical mediator release, and comorbidities.
  • Current management involves escalating epinephrine (e.g., intravenous) and adjunctive therapies, but guidelines are inconsistent.

Conclusions:

  • Clear protocols are needed for recognizing and managing refractory anaphylaxis, including escalation of care and use of intravenous epinephrine or adjunctive agents.
  • Standardized diagnostic criteria and prospective studies are essential to understand risk factors, outcomes, and optimal strategies.
  • Further research into biomarkers and novel therapies is warranted for early identification and improved treatment of high-risk cases.