Roy Khalaf , Connor Prosty MD , William Davalan , Elissa Abrams MD , Mohammed Kaouache PhD , Moshe Ben-Shoshan MD
{"title":"Diagnostic Utility of Biomarkers in Anaphylaxis: A Systematic Review and Meta-Analysis","authors":"Roy Khalaf , Connor Prosty MD , William Davalan , Elissa Abrams MD , Mohammed Kaouache PhD , Moshe Ben-Shoshan MD","doi":"10.1016/j.jaip.2025.04.008","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Objective</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":51323,"journal":{"name":"Journal of Allergy and Clinical Immunology-In Practice","volume":"13 6","pages":"Pages 1342-1349.e12"},"PeriodicalIF":8.2000,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Allergy and Clinical Immunology-In Practice","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2213219825003629","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ALLERGY","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍:
JACI: In Practice is an official publication of the American Academy of Allergy, Asthma & Immunology (AAAAI). It is a companion title to The Journal of Allergy and Clinical Immunology, and it aims to provide timely clinical papers, case reports, and management recommendations to clinical allergists and other physicians dealing with allergic and immunologic diseases in their practice. The mission of JACI: In Practice is to offer valid and impactful information that supports evidence-based clinical decisions in the diagnosis and management of asthma, allergies, immunologic conditions, and related diseases.
This journal publishes articles on various conditions treated by allergist-immunologists, including food allergy, respiratory disorders (such as asthma, rhinitis, nasal polyps, sinusitis, cough, ABPA, and hypersensitivity pneumonitis), drug allergy, insect sting allergy, anaphylaxis, dermatologic disorders (such as atopic dermatitis, contact dermatitis, urticaria, angioedema, and HAE), immunodeficiency, autoinflammatory syndromes, eosinophilic disorders, and mast cell disorders.
The focus of the journal is on providing cutting-edge clinical information that practitioners can use in their everyday practice or to acquire new knowledge and skills for the benefit of their patients. However, mechanistic or translational studies without immediate or near future clinical relevance, as well as animal studies, are not within the scope of the journal.