Rash decisions: Unmasking a risk phenotype in adults with persistent delayed penicillin allergy sensitized during historic infection with Epstein-Barr virus

Abstract

BackgroundPenicillin-associated exanthems in the setting of infectious mononucleosis (IM) caused by Epstein-Barr virus (EBV) are often viewed as a transient event, and not a true allergy. Recent evidence challenges this and suggest a notable subset of patients retain penicillin hypersensitivity. ObjectiveWe investigated the occurrence and predictors of persistent adulthood hypersensitivity in those with a penicillin-associated rash occurring in the setting of EBV infection. MethodRetrospective analysis of patients referred for penicillin allergy testing to an Australian tertiary hospital captured from 2015 to 2023 was carried out. ResultsOf 2,066 patients, 23 (1%) had a penicillin-associated rash during an historic EBV infection; 16 (70%) female, median 18 years (interquartile range [IQR] 16-20) at index reaction, median 38 years (IQR 33.5-57) when allergy tested. Skin-prick and delayed-intradermal testing (D-IDT) to a penicillin panel were performed and oral provocation challenge in those testing negative. Persistent sensitisation was shown in 6/23 (26%); 4/6 (67%) positive D-IDT, 3/6 (50%) positive oral challenge. Notably, 5/6 (83%) had a severe maculopapular exanthem (sMPE) with facial swelling, including 2/6 (33%) with probable drug reaction with eosinophilia and systemic symptoms (DRESS) during the index reaction, compared with 0/17 (0%) in patients tolerating penicillin on re-exposure. ConclusionThis study highlights the requirement of allergy testing in adult patients reporting a penicillin-associated sMPE in the setting of EBV, even if occurring during childhood or adolescence.