A Retrospective Critical Analysis and Risk Stratification of Penicillin Allergy De-labelling in a UK Specialist Regional Allergy Service.

BACKGROUND A spurious label of penicillin allergy (Pen-A) negatively impacts on antibiotic stewardship and healthcare costs. Recent studies have proposed a guideline-steered direct penicillin challenge without undertaking allergy tests when 'true allergy' is unlikely. OBJECTIVE Critically analyse Pen-A clinical presentation, perform risk stratification and determine clinical predictors for 'true allergy'. METHOD Retrospective data extraction from clinical and electronic patient records. RESULTS 231 patients (M= 82; F=149; mean age 51.22 (SD ± 18.07 years) were analysed. Based on clinical history, patients were categorised as likely type I hypersensitivity [HSR] (n=27), likely type IV HSR (n=65), indeterminate (n=111) and HSR unlikely (n=28). Based on index reaction and co-morbidities, patients were classified into 'low risk' (n=143) and 'high risk' (n=78). Pen-A was excluded in 74% of patients assessed having likely type I HSR, 91% with likely type IV HSR, 93% of indeterminate and 100% of HSR unlikely patients. Negative predictive value for successful de-labelling in the 'low risk' group was 94% (odds ratio [OR] - 2.9; p= 0.02). Predictors for 'true Pen-A' were history of anaphylaxis (OR - 30.6; p < 0.001), hospitalization (OR - 7; p<0.001), ≤5 years since index reaction (OR - 3; p= 0.04). CONCLUSION Systematic clinical characterisation and risk stratification has an important role in Pen-A de-labelling. These data provide proof of concept for a guideline-based selection of patients labelled with Pen-A for a direct penicillin challenge. Patients in the 'low risk' group seem suitable for this intervention, although a rigorous prospective evaluation is needed in a multi-centre study

Empty mast cell syndrome: fallacy or fact?

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