Specific IgE to penicillin minor determinants in patients with suspected penicillin allergy

To the Editor, Risk stratification of patients with suspected penicillin allergy is an important tool in identifying patients with immediate type reactions, who may carry a high risk of a reaction during allergy investigations with skin testing and/or drug provocation testing. In this patient category invitro tests such as measurement of specific IgE to penicillins may be a safer first step investigation and this has been recommended in recent European Guidelines.1 A recent metaanalysis on the accuracy of specific IgE as a diagnostic test in penicillin allergy, including studies of both immediate and nonimmediate reactions, reported a high specificity (97.4%) but low sensitivity (19.3%).2 Due to the reported low sensitivity, specific IgE is not utilized in many countries and experience in the literature is limited. In Denmark, tests for specific IgE to penicillins have been used routinely for many years in penicillin allergy investigation. Danish guidelines from 2006 recommended measuring specific IgE in all patients referred for penicillin allergy investigation. Guidelines were updated in 2019 and current recommendations are to only measure specific IgE to penicillins in patients with immediate type reactions. Elevated specific IgE to one or more penicillins is considered diagnostic in the context of a clear history of an immediate type reaction. Thus, patients with immediate type reactions will only proceed to skin testing and a titrated drug provocation test if specific IgE towards penicillins are negative (<0.35 kUA/L). The specific IgE assays available in the Allergy Clinic in Gentofte Hospital are penicillin V/phenoxymethylpenicillin (PV), penicillin G/benzylpenicillin (PG), amoxicillin (AMX) and ampicillin (AMP). In addition, the department has routinely performed specific IgE to penicillin minor determinants (MD). The ImmunoCAP Penicillin MD test was developed using


Specific IgE to penicillin minor determinants in patients with suspected penicillin allergy
To the Editor, Risk stratification of patients with suspected penicillin allergy is an important tool in identifying patients with immediate type reactions, who may carry a high risk of a reaction during allergy investigations with skin testing and/or drug provocation testing. In this patient category in-vitro tests such as measurement of specific IgE to penicillins may be a safer first step investigation and this has been recommended in recent European Guidelines. 1 A recent meta-analysis on the accuracy of specific IgE as a diagnostic test in penicillin allergy, including studies of both immediate and non-immediate reactions, reported a high specificity (97.4%) but low sensitivity (19.3%). 2 Due to the reported low sensitivity, specific IgE is not utilized in many countries and experience in the literature is limited. In Denmark, tests for specific IgE   Penicillin V and designed to keep the bicyclic beta lactam-thiazolidine structure intact and hence, measuring specific IgE to minor epitopes.
The MD specific IgE assay was initially available to the clinic on a research basis but is now commercially available in some countries. All assays are using the ImmunoCAP technology (ThermoFisher Scientific).
In this study, we aimed to identify the proportion of patients with suspected penicillin allergy where specific IgE to penicillins is elevated and to evaluate if patients with elevated specific IgE to minor determinants differ clinically from patients with elevated specific IgE to one or more other penicillins.
Approval to retrieve data with exemption from informed patient were mono-sensitized to MD, 75 (17.2%) mono-sensitized to PV, 4 (0.9%) to PG, 12 (2.8%) to AMX and 9 (2.1%) to AMP. history, has previously been shown to be predictors of a clinically significant allergy. 3,4 As IgE sensitization does not always correspond to clinical allergy, IgE levels should only be interpreted in the context of a relevant clinical history with an immediate type reaction, and thereby improving specificity. It has been suggested that in patients with very severe immediate type reactions, elevated specific IgE to one or more penicillins may be considered diagnostic, avoiding the need for confirmatory tests such as skin testing or drug provocation which may induce systemic reactions. 1,5 No other studies evaluating the specific IgE MD assay could be identified in the literature. However, several studies discuss penicillin minor determinants in skin testing and argue that skin tests with minor determinants are essential in evaluating suspected penicillin allergy as the two Penicillin V metabolites, penicilloate and penilloate, are important factors in inducing allergic responses. 6,7 Other studies suggest that minor determinants derived from amoxicillin does not perform better than skin test with AMX or PG alone. 8,9 Findings in our study are not validated by skin testing or drug provocation testing which is a limitation as this means that sensitivity and specificity cannot be assessed. Also, 2/3 of patients with

DATA AVA I L A B I L I T Y S TAT E M E N T
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.