Validation of the PEN-FAST Clinical Decision Rule for Penicillin Allergy in an Irish Cohort: A Retrospective Study

Penicillin allergy labels remain common and clinically consequential, despite most being inaccurate when formally evaluated. The PEN-FAST clinical decision rule identifies patients at low risk of true penicillin allergy who may safely undergo direct oral challenge without prior skin testing. We aimed to evaluate the performance of PEN-FAST in an Irish cohort undergoing penicillin allergy assessment.

We retrospectively reviewed adults assessed for reported penicillin allergy in a tertiary immunology day-ward service between January 2020 and December 2024. PEN-FAST scores were calculated from clinical documentation. All patients underwent supervised oral penicillin challenge. Diagnostic performance of the established low-risk threshold (<3) was assessed.

A total of 142 patients were included (mean age 48 years; 73% female), of whom 108 (76%) were classified as low risk. Five patients (3.5%) had positive oral challenges. Three of these had PEN-FAST scores <3. All reactions in the low-risk group were mild delayed maculopapular exanthems; no immediate hypersensitivity reactions, anaphylaxis, or severe cutaneous adverse reactions occurred. Among low-risk patients, 105 of 108 (97.2%) tolerated challenge, yielding a negative predictive value (NPV) of 97% (95% CI, 92-99).

In this European cohort, PEN-FAST demonstrated a high negative predictive value for immediate hypersensitivity reactions to penicillin. Mild delayed reactions occurred in a small minority of low-risk patients but were non-severe. These findings support implementation of PEN-FAST-guided direct oral challenge within structured penicillin allergy de-labelling pathways.