Direct Oral Challenge is Non-inferior to Skin Testing in Low-risk Penicillin Allergy Patients
Clinical question: Is there an alternative to penicillin skin testing for low-risk penicillin allergies?
Dr. Miller
Background: While approximately 10% of the population report penicillin allergies, studies indicate that more than 95% of these individuals will have negative allergy testing and can tolerate penicillin. The current gold standard for relabeling a penicillin allergy involves skin testing followed by direct oral challenge. However, specialized allergy skin testing is not universally accessible, and can be labor-intensive and costly. Moreover, skin testing alone doesn’t conclusively demonstrate penicillin tolerance.
Study design: Multicenter, open-label, randomized, controlled trial
Setting: Six large academic centers in three countries
Synopsis: 382 outpatient adults labeled with a reported penicillin allergy were assessed using the PEN-FAST scoring system. Those with a PEN-FAST score of less than 3 and no history of anaphylaxis were eligible. Participants were randomized to either intradermal testing followed by direct oral challenge or direct oral challenge alone. The primary outcome showed one patient in each intervention group experienced immune-mediated reactions, both managed with a single dose of an oral antihistamine. Limitations include lower PEN-FAST scores for almost all enrollees (scores of 0-1) and an exclusion of patients with a history of anaphylaxis. In addition, most of the participants were white, limiting the study’s generalizability to other racial demographics. For hospitalists, our patients have ample time and baseline supervision to undergo this testing more easily than other health care contacts.
Bottom line: Direct oral challenge for low-risk penicillin-allergic patients using the PEN-FAST tool is non-inferior to the current practice of skin testing prior to oral challenge.
Citation: Copaescu AM, et al. Efficacy of a clinical decision rule to enable direct oral challenge in patients with low-risk penicillin allergy: The PALACE randomized clinical trial. JAMA Intern Med. 2023. doi:10.1001/jamainternmed.2023.2986
Dr. Miller is an academic hospitalist and associate professor of medicine in the department of hospital medicine at the University of New Mexico Hospital, Albuquerque, N.M