title: A 17-year experience in perioperative anaphylaxis 1998-2015: harmonizing optimal detection of mast cell mediator release.
abstract: Sheffield NARCOS (National Adverse Reactions Advisory Service) investigates suspected perioperative anaesthetic reactions using serial tryptase, urinary methylhistamine (UMH) and clinical information. Further recommendations for additional allergy clinic assessment are provided.
  
  
  
  To establish a robustly measurable protocol for identifying mast cell mediator (MMR) release in this cohort. To compare these thresholds with previously suggested thresholds and algorithms.
  
  
  
  A review of 3455 NARCOS cases referred with a suspected perioperative allergic reaction. Tryptase, UMH and clinical details were analysed. A total of 1746 cases were graded using the Ring and Messmer scale. Reaction grade, tryptase and UMH changes were compared with statistical and graphical presentations appropriate to non-normally distributed measurements using Analyse-IT software.
  
  
  
  Sensitive strategies such as 3 μg/L or 20% are measurable and translatable and would substantially increase detection of potentially relevant changes in tryptases. Adequate quality assurance for low-level measurement is needed. An incremental threshold of 20% would identify potential MMR in an additional 14% of cases with peak tryptase (Tp) between 5 and 14 μg/L and a further 15% with Tp below 5 μg/L. Further work is required to establish the diagnostic performance characteristics of this more sensitive approach. UMH also identified up to 120 further cases of potential MMR in the absence of tryptase increments.
  
  
  
  Future studies should establish and compare the predictive performance characteristics of each strategy against clinical phenotypes. A single agreed definition of positive serial tryptases is needed to enable robust evaluation of diagnostic strategies. This could serve as a harmonized standard for comparative studies of case series from different centres.
authors.affiliation: Clinical Immunology and Allergy Unit and Department of Immunology and Protein Reference Unit, Sheffield Teaching Hospitals NHS Trust, Sheffield, UK. william.egner@sth.nhs.uk.
authors.forename: W
authors.initials: W
authors.lastname: Egner
authors.affiliation: Clinical Immunology and Allergy Unit and Department of Immunology and Protein Reference Unit, Sheffield Teaching Hospitals NHS Trust, Sheffield, UK.
authors.forename: R
authors.initials: R
authors.lastname: Sargur
authors.affiliation: Clinical Immunology and Allergy Unit and Department of Immunology and Protein Reference Unit, Sheffield Teaching Hospitals NHS Trust, Sheffield, UK.
authors.forename: A
authors.initials: A
authors.lastname: Shrimpton
authors.affiliation: Clinical Immunology and Allergy Unit and Department of Immunology and Protein Reference Unit, Sheffield Teaching Hospitals NHS Trust, Sheffield, UK.
authors.forename: M
authors.initials: M
authors.lastname: York
authors.affiliation: Clinical Immunology and Allergy Unit and Department of Immunology and Protein Reference Unit, Sheffield Teaching Hospitals NHS Trust, Sheffield, UK.
authors.forename: K
authors.initials: K
authors.lastname: Green
mesh_terms: D000707:Anaphylaxis / Q000175:diagnosis / Q000453:epidemiology* / Q000209:etiology* / Q000266:history; D015415:Biomarkers; D016207:Cytokines / Q000378:metabolism; D005260:Female; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism; D008761:Methylhistamines / Q000652:urine; D059035:Perioperative Period; D012720:Severity of Illness Index; D013997:Time Factors; D053802:Tryptases / Q000097:blood
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D008761:Methylhistamines; D053802:Tryptases
keywords: allergy; anaesthesia; anaphylaxis; human; mast cells; perioperative