Diagnostic Utility of Biomarkers in Anaphylaxis: A Systematic Review and Meta-Analysis.

Background: Anaphylaxis is a life-threatening allergic reaction commonly triggered by food, venom, or drugs. Clinical criteria are central to diagnosing anaphylaxis. However, laboratory biomarkers could provide valuable confirmation when clinical diagnosis is challenging.

Objective: We aimed to evaluate key biomarkers including tryptase, histamine, platelet-activating factor (PAF), PAF-acetylhydrolase (PAF-AH), and urinary prostaglandin D2 (PGD2) for their diagnostic utility in anaphylaxis.

Methods: A systematic review was conducted following PRISMA-DTA (Preferred Reporting Items for a Systematic Review and Meta-analysis of Diagnostic Test Accuracy studies) guidelines. Studies published between 2004 and 2024 from Embase and MEDLINE were included if they evaluated the diagnostic test accuracy of tryptase, histamine, PAF, PAF-AH, or urinary PGD2 in confirmed anaphylaxis cases. Pooled sensitivity and specificity estimates were calculated using the diagmeta package in R.

Results: Twenty-eight studies with 18,749 patients were included, of whom 3329 had anaphylaxis. Tryptase was the most frequently studied biomarker (24 studies), with a pooled sensitivity and specificity of 0.49 and 0.82, respectively. Histamine had a pooled sensitivity of 0.76 and a specificity of 0.69. Limited data were available for PAF, PAF-AH, and urinary PGD2.

Conclusions: Studies suggest that tryptase remains the most widely used and accessible biomarker for diagnosing anaphylaxis mainly using the "Rule of Twos" diagnosis strategy. Histamine and urinary PGD2 show potential, though their application is limited by practical challenges. Further research is needed to establish the diagnostic roles of PAF and PAF-AH, particularly in non-IgE-mediated anaphylaxis pathways.