Original ArticlesAsthma, Lower Airway DiseasesSkin testing only with penicillin G in children with a history of penicillin allergy
Introduction
Approximately 5% of children and 10% of adults report a history of penicillin allergy, although only a few of these patients are truly allergic.[1], [2], [3], [4] Because history is a poor predictor of reactivity, penicillin allergy evaluation that consists of skin tests, often followed by a drug challenge, is key to identify truly allergic and nonallergic patients who can be safely treated with penicillins.[5], [6] The importance of evaluating patients with a history of penicillin allergy is increasingly recognized given that penicillin avoidance is unnecessary for most of them and leads to the use of alternative broader-spectrum antibiotics (vancomycin and fluoroquinolones), which have been associated with additional costs and significant morbidities, such as vancomycin-resistant enterococcus and Clostridium difficile–associated diarrhea.[2], [7], [8], [9]
Skin test reagents used for penicillin allergy evaluation include penicilloyl-polylysine (PPL), the major antigenic determinant, and a variety of minor determinants, the most commonly used being penicillin G.[6], [10] After a negative skin test result, a drug challenge is often performed because, depending on the population studied and skin test reagents used, up to 31% of patients require a drug challenge to identify their allergy.11 A drug challenge may also provide reassurance to patients and parents who might not be convinced that they are not allergic based on negative skin test results and may therefore continue to avoid penicillins.[12], [13]
The lack of commercially available PPL for most of the last decade in North America seriously hampered the practice of penicillin allergy evaluation.[4], [14] Skin testing without PPL is not recommended because up to 75% of patients who have a positive skin test react only to PPL; therefore, only a few allergists who had the capacity to produce their own skin test reagents were apt to perform penicillin allergy evaluation during this time.[4], [6], [15] Some groups proposed alternative approaches to palliate the absence of PPL, such as combining penicillin G skin testing with radioallergosorbent testing to PPL followed by 2 graded challenges, but none reached consensus, and in many cases the practice was abandoned.[4], [16], [17]
Given the importance of penicillin allergy evaluation, especially in patients with frequent infections and/or a history of allergic reactions to multiple antibiotics, the decision was made at our institution to perform penicillin allergy evaluation in the absence of PPL using only penicillin G for skin testing followed, if results were negative, by a 3-dose graded challenge to the penicillin incriminated in the initial allergic reaction. Preliminary results revealing a low reaction rate after a negative penicillin G skin test result led us to adopt this approach as standard practice at our institution until PPL recommericalization.18 The aim of this study was to determine the safety of this approach and the negative predictive value (NPV) of skin testing solely with penicillin G for predicting an IgE-mediated penicillin allergy.
Section snippets
Study Cohort
The study was performed at the CHU Sainte-Justine, a large Canadian pediatric university hospital, and was approved by the CHU Sainte-Justine Institutional Review Board. Written informed consent was obtained from parents or legal tutors and/or patients at the time of evaluation. All patients who underwent penicillin skin testing between December 2006 and December 2009 at the CHU Sainte-Justine Allergy Clinic were identified by medical record review. Patients with a history of reaction to any
Results
A total of 563 patients with a history of penicillin allergy were skin tested to penicillin G between December 2006 and December 2009 (Table 1). Patients were between 7 months and 21 years of age (median age, 5.8 years) at the time of evaluation, and 51% were female. Twenty-eight percent had a history of atopy and 17% had a history of asthma in line with estimates of the prevalence of these conditions in the pediatric population.[20], [21] Most patients (89%) reported a reaction to amoxicillin
Discussion
In a pediatric cohort of 563 patients with a history of penicillin allergy, the results of skin testing only with penicillin G (in the absence of PPL) were positive in 33% and yielded a NPV of 95.2% (95% CI, 92.5%–97.1%) based on challenge outcomes. After a negative penicllin G skin test result, a 3-dose graded challenge to the incriminated penicillin was found to be safe, even in patients with a history of anaphylaxis, because no patient experienced a severe reaction as a result. To our
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Cited by (23)
Diagnosis and selection of alternative antibiotics in beta-lactams hypersensitivity reactions: Current recommendations and challenges
2023, International ImmunopharmacologyPenicillin Allergy: Mechanisms, Diagnosis, and Management
2023, Primary Care - Clinics in Office PracticePediatric Drug Allergy
2022, Immunology and Allergy Clinics of North AmericaCitation Excerpt :For patients with a history of anaphylaxis or SCAR to beta-lactams, direct ingestion challenge is contraindicated. A negative skin test should be elicited before direct ingestion challenge in patients with a history of anaphylaxis to beta-lactams.21,30 Because of low cross-reactivity between penicillin derivatives and cephalosporins, most cases of true penicillin allergy can safely be administered cephalosporins with dissimilar side chains.31
Direct Challenges for the Evaluation of Beta-Lactam Allergy: Evidence and Conditions for Not Performing Skin Testing
2021, Journal of Allergy and Clinical Immunology: In PracticeCitation Excerpt :When retested a year later, 33% were found to be ST-negative.34 Picard et al35 showed a 38% (n = 63/165) positive ST rate in those with penicillin reactions within the past 0.9 years. This rate declined to 25% (n = 17/68) in those with penicillin reaction 10 to 17 years prior.
Accuracy of penicillin allergy diagnostic tests: A systematic review and meta-analysis
2021, Journal of Allergy and Clinical ImmunologyCitation Excerpt :Of the 122 articles meeting the eligibility criteria, 17 were excluded because some participants had also been assessed (receiving the same tests) by studies assessing larger samples. Therefore, a total of 105 studies were included in this systematic review.13,22-125 For studies in which some degree of participant overlap with other study(ies) occurred (see Table E2 in this article’s Online Repository at www.jacionline.org),36,37,40-42,59,62,69,72,83,106,109 we presented only unique information from each study (eg, results from diagnostic tests performed in 1 study that had not been performed in the other study assessing the same participants), so that no participant has been included more than once.
Children with reported penicillin allergy: Public health impact and safety of delabeling
2020, Annals of Allergy, Asthma and ImmunologyCitation Excerpt :Alternative methods of skin testing have also been explored and proved to be an effective way to address reported penicillin allergy in children. Picard et al23 evaluated the safety and NPV of skin testing with only penicillin G followed by a 3-dose graded challenge to the incriminated penicillin. In a 3-year period, they skin tested 563 patients aged 7 months to 21 years with penicillin G, and 185 (33%) had a positive skin result.
Disclosures: Authors have nothing to disclose.