Available online 21 March 2023

Previous data suggest up to one-third of patients classified as allergic based on positive penicillin skin tests have a vague reaction history. Direct oral challenge (DOC) has been recommended for patients with a low-risk reaction history. A variety of published models stratify reaction risk to guide the use of DOC.

To re-assess the proportion of penicillin skin test positive patients with vague or low-risk reaction histories, and evaluate the relationship between reaction risk history and likelihood of positive skin test results.

We identified patients who underwent penicillin allergy evaluation over a 5-year period. We recorded drug reaction history, demographic variables, skin testing and challenge results. Matched controls whose skin tests were negative were identified for skin test positive patients. Drug reaction histories were assigned a risk category based on two previously published risk stratification models. We used logistic regression to investigate whether reaction history risk was associated with positive skin test results.

Penicillin skin testing was performed in 3,382 patients; 207 (6.1%) were positive. Positive skin tests were more frequent in outpatients (p<0.001), younger (p<0.001), and female patients (p<0.001). Percentages of each risk category in each model were similar in cases vs. matched controls. Likelihood for positive skin tests increased with a high-risk reaction history in one stratification model.

Our data confirm a substantial proportion of patients who self-report penicillin allergy and have positive skin test results have a low-risk history, and imply penicillin skin testing is associated with a poor positive predictive value.

© 2023 Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology