Using biomarkers for anaphylaxis diagnosis

Published online April 13, 2025

Diagnosing anaphylaxis remains a clinical challenge due to a broad number of conditions with similar symptoms. To assist in confirming diagnoses, several biomarkers have been proposed, but their reliability varies widely. 

In this systematic review and meta-analysis published in The Journal of Allergy and Clinical Immunology: In Practice, Khalaf et al. explore the diagnostic accuracy of five biomarkers including tryptase, histamine, platelet-activating factor (PAF), PAF-acetylhydrolase (PAF-AH), and urinary prostaglandin D2 (PGD2) to evaluate their clinical utility in anaphylaxis diagnosis. The authors, under the supervision of senior author Dr Ben-Shoshan, identified 28 studies encompassing over 18,000 patients, of whom 3,329 had confirmed anaphylaxis. They evaluated the pooled sensitivity and specificity of each biomarker. Subgroup analyses were conducted for age groups, anaphylaxis triggers (e.g., food vs. perioperative), and biomarker cutoff strategies, including the “Rule of Twos” for tryptase.

Tryptase, the most studied biomarker, showed moderate specificity (0.82) but limited sensitivity (0.49), suggesting a high rate of false negatives. Histamine performed better in sensitivity (0.76) but was less specific (0.69). While PAF and PAF-AH have shown theoretical promise due to their roles in the inflammatory cascade, clinical data were limited. Urinary PGD2 exhibited high specificity (0.95) in pediatric food challenge studies but lacks widespread applicability due to collection constraints. The authors concluded that while tryptase remains the most practical marker, none of the biomarkers should replace clinical judgment, especially in cases with uncertain triggers or atypical presentations.

The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.

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