SummaryThis is the first multi-centre retrospective survey from the United Kingdom to evaluate the aetiology and diagnostic performance of tryptase in anaphylaxis during general anaesthesia (GA). Data were collected retrospectively (2005-12) from 161 patients [mean ± standard deviation (s.d.), 50 ± 15 years] referred to four regional UK centres. Receiver operating characteristic curves (ROC) were constructed to assess the utility of tryptase measurements in the diagnosis of immunoglobulin (Ig)E-mediated anaphylaxis and the performance of percentage change from baseline [percentage change (PC)] and absolute tryptase (AT) quantitation. An IgE-mediated cause was identified in 103 patients (64%); neuromuscular blocking agents (NMBA) constituted the leading cause (38%) followed by antibiotics (8%), patent blue dye (6%), chlorhexidine (5%) and other agents (7%). In contrast to previous reports, latex-induced anaphylaxis was rare (0·6%). A non-IgE-mediated cause was attributed in 10 patients (6%) and no cause could be established in 48 cases (30%). Three serial tryptase measurements were available in 34% of patients and a ROC analysis of area under the curve (AUC) showed comparable performance for PC and AT. A ≥ 80% PPV for identifying an IgEmediated anaphylaxis was achieved with a PC of >141% or an AT of >15·7 mg/l. NMBAs were the leading cause of anaphylaxis, followed by antibiotics, with latex allergy being uncommon. Chlorhexidine and patent blue dye are emerging important health-care-associated allergens that may lead to anaphylaxis. An elevated acute serum tryptase (PC >141%, AT >15·7 mg/l) is highly predictive of IgE-mediated anaphylaxis, and both methods of interpretation are comparable.

There is no standardized method for assessing serum total mast cell tryptase (MCT) in anaphylaxis. The consensus equation (peak MCT should be>1.2× baseline tryptase+2 mg/L) has been proposed to interpret acute MCT in mast cell activation syndrome (MCAS). To validate consensus equation in a perioperative setting analyses of cases of suspected perioperative anaphylaxis during general anaesthesia (GA) were performed. Anaphylaxis was defined as per World Allergy Organisation (WAO) criteria. Timed serial MCT measurements were mapped against the consensus equation and receiver operating characteristic (ROC) curves produced. A total of 82 patients (60 females, mean age 56.5 years±SD17.2) underwent investigation. Sixty (73%) patients fulfilled WAO criteria for anaphylaxis, and 22 patients did not. Aetiology included 59% IgE-mediated anaphylaxis, 2% non-IgE-mediated anaphylaxis, 12% anaphylaxis of unknown cause and 27% deemed non-anaphylaxis. IgE-mediated anaphylaxis included the following: NMBA (35%), antibiotics (46%), chlorhexidine (8%), patent blue dye (8%) and others (8%). An acute MCT with a comparable baseline was available in 71 of 82 (87%) patients (60 anaphylaxis and 11 controls). The median interquartile range (IQR) time from reaction to peak MCT was 1.34 (0.82-2.51) hours. Analyses confirmed that a rise in acute MCT greater than that defined by the equation had a sensitivity, specificity, positive predictive value (PPV) and negative (N) PV of 78%, 91%, 98% and 44%, respectively. The magnitude of increase in acute MCT above the threshold predicted by consensus equation was higher in the anaphylaxis group compared to controls (P=.0001). This equation has a high specificity, PPV with a moderate NPV and sensitivity in perioperative anaphylaxis.

The new PPL and MDM determinants offer enhanced sensitivity when evaluating β-lactam hypersensitivity; however, there are limitations to the current testing regimens. The UK would benefit from local guidelines, which incorporate the new reagents and acknowledge the high amoxicillin prescription rate and the relatively lower specialist-to-patient ratio in this country.

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Post-anaphylaxis mast cell anergy (PAMA), commonly referred to as ‘empty mast cell (MC) syndrome’, is a state of temporary loss of cutaneous MC reactivity in the immediate aftermath of anaphylaxis. Data relating to this condition are sparse and the incidence rate is currently unknown. PAMA has been described only in a few published case reports in the context of hymenoptera venom allergy and perioperative anaphylaxis. Best practice guidelines regarding optimal timing for performing skin tests postanaphylaxis are largely based on expert opinion, and allergy work-up has been recommended after 4–6 weeks postanaphylaxis to avoid false-negative results.This article provides a review of clinical literature surrounding PAMA, critically evaluates intracellular events in MCs from in vitro data and hypothesises regarding plausible immune mechanisms. There are no published data to directly explain molecular mechanisms underlying this phenomenon. Although not evidence based, PAMA has been attributed to depletion of MC granules following anaphylaxis. It is also plausible that exposure to high allergen concentrations in anaphylaxis can induce a temporary shift in MCs towards dominance of inhibitory signalling pathways, thus contributing to a state of transient hyporesponsiveness observed in some patients. Other potential contributory factors for reduced MC reactivity include downregulation of FcεRI expression, cross-linking of FcεRI to the inhibitory, low-affinity IgG receptors and administration of pharmacotherapeutic agents for anaphylaxis treatment. It is likely that this interesting phenomenon can be explained by a combination of these proposed mechanisms in addition to other genetic/host factors that have not yet been identified.