Anaphylaxis and clinical utility of real-world measurement of Acute Serum Tryptase in UK emergency departments

Background: British guidelines recommend that serial acute serum tryptase measurements be checked in all adults and a subset of children presenting with anaphylaxis. This is the first study reporting the clinical utility of acute serum tryptase in a “real-world” emergency department (ED) setting following the publication of the World Allergy Organization (WAO) criteria for anaphylaxis. Objectives: To (1) assess sensitivity, specificity, and positive and negative predictive values (PPV, NPV) of acute serum tryptase in anaphylaxis; (b) determine factors associated with higher acute serum tryptase levels; and (c) audit compliance of acute serum tryptase measurement in the ED. Methods: The methods used were retrospective electronic search for ED admissions to 3 acute care hospitals in Birmingham, UK, with anaphylaxis in 2012 using wide search terms followed by scrutiny of electronic clinical records and application of the WAO diagnostic criteria for anaphylaxis. Patients with an acute serum tryptase measurement were included in the analysis. Results: Acute serum tryptase level was measured in 141 of 426 (33.1%) cases. Mean time from the onset of symptoms to the measurement of acute serum tryptase level was 4 hours 42 minutes (SD ± 05:03 hours) and no patients had serial measurements conforming to British guidelines. Acute serum tryptase level of more than 12.4 ng/mL (75th centile) was associated with a sensitivity, specificity, PPV, and NPV of 28%, 88%, 0.93, and 0.17, respectively. Multiple regression analysis showed that male sex (odds ratio, 2.66; P = .003) and hypotension (odds ratio, 7.08; P = .001) predicted higher acute serum tryptase level. Conclusions: An acute serum tryptase level of more than 12.4 ng/mL in an ED setting carries high PPV and specificity, but poor sensitivity and NPV

A 17 year experience in perioperative anaphylaxis 1998-2015: harmonising optimal detection of mast cell mediator release.

BACKGROUND: Sheffield NARCOS (National Adverse Reactions Advisory Service) investigates suspected perioperative anaesthetic reactions using serial tryptase, urinary methylhistamine and clinical information. Further recommendations for additional allergy clinic assessment are provided. OBJECTIVE: To establish a robustly measurable protocol for identifying mast cell mediator (MMR) release in this cohort. To compare these thresholds with previous suggested thresholds and algorithms. METHOD: A review of 3,455 NARCOS cases referred with a suspected peri-operative allergic reaction. Tryptase, Urinary methylhistamine (UMH) and clinical details were analysed. 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. RESULTS: Sensitive strategies such as 3μg/l or 20% are measurable, 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 absence of tryptase increments. CONCLUSION AND CLINICAL RELEVANCE: 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 harmonised standard for comparative studies of case series from different centres. This article is protected by copyright. All rights reserved

2015 update of the evidence base:World Allergy Organization anaphylaxis guidelines

The World Allergy Organization (WAO) Guidelines for the assessment and management of anaphylaxis provide a unique global perspective on this increasingly common, potentially life-threatening disease. Recommendations made in the original WAO Anaphylaxis Guidelines remain clinically valid and relevant, and are a widely accessed and frequently cited resource. In this 2015 update of the evidence supporting recommendations in the Guidelines, new information based on anaphylaxis publications from January 2014 through mid- 2015 is summarized. Advances in epidemiology, diagnosis, and management in healthcare and community settings are highlighted. Additionally, new information about patient factors that increase the risk of severe and/or fatal anaphylaxis and patient co-factors that amplify anaphylactic episodes is presented and new information about anaphylaxis triggers and confirmation of triggers to facilitate specific trigger avoidance and immunomodulation is reviewed. The update includes tables summarizing important advances in anaphylaxis research. Keywords: Anaphylaxis, Epinephrine, Auto-injector, Food allergy, Stinging insect venom allergy, Drug allergy, Latex allergy, Exercise-induced anaphylaxis, Systemic allergic reaction, Adrenalin

Diagnostic value of tryptase in food allergic reactions: a prospective study of 160 adult peanut challenges

Background: Serum tryptase is useful in diagnosing drug and venom anaphylaxis. Its utility in food anaphylaxis is unknown. Objective: The objective of this study was to determine whether tryptase rises in food allergic reactions, optimal sampling time points, and a diagnostic cutoff for confirming a clinical reaction. Methods: Characterized peanut allergic patients were recruited and underwent up to 4 peanut challenges and 1 placebo challenge each. Tryptase was measured serially on challenge days both before (baseline) and during the challenge. The peak percentage tryptase rise (peak/baseline) was related to reaction severity. Receiver operating characteristic (ROC) curves were generated establishing an optimal diagnostic cutoff. Results: Tryptase was analyzed in 160 reactive (9% anaphylaxis) and 45 nonreactive (placebo) challenges in 50 adults aged 18 to 39 years. Tryptase rose above the normal range (11.4 ng/mL) in 4 of 160 reactions. When compared with baseline levels, a rise was observed in 100 of 160 (62.5%) reactions and 0 of 45 placebo challenges. The median rise (95% confidence interval [CI]) for all reactions was 25% (13.3% to 33.3%) and 70.8% (33.3% to 300%) during anaphylaxis. Peak levels occurred at 2 hours and correlated with severity (P <.05). Moderate-to-severe respiratory symptoms, generalized erythema, dizziness, and hypotension were correlated with a higher peak/baseline tryptase (P <.05). ROC curve analysis demonstrated the optimal cutoff to identify a reaction as a 30% rise (sensitivity 0.53; specificity 0.85), area under the curve 0.72 (95% CI, 0.67-0.78). Conclusions: Serum tryptase measurement is valuable in food allergic reactions, and correlates with symptom severity. Comparing peak reaction levels at 2 hours with baseline is essential. A rise in tryptase of 30% is associated with food allergic reactions

Post mortem tryptase: A review of literature on its use, sampling and interpretation in the investigation of fatal anaphylaxis.

Post mortem tryptase is a commonly-used ancillary test in the investigation of possible anaphylactic deaths. Ante mortem tryptase interpretation differs from post mortem interpretation due to differing priorities, biochemical behaviours and capacity for follow-up. Additionally, post mortem tryptase sampling site, method and even cut-off levels are not standardised between facilities. This review of the literature investigates the existing research and recommendations on the use of post mortem tryptase in suspected anaphylactic deaths. Currently, autopsy recommendations suggest early sampling, standardised sampling technique with clamping of and aspiration from the femoral vein, and for the results to be interpreted within the wider autopsy and clinical context. Areas in need of further research include the effects of cytolysis on tryptase levels and studies to stratify differing tryptase levels based on type of death and anaphylactic trigger