Penicillin Allergy?

Is that penicillin or amoxicillin allergy real? Probably not. In this episode, we explore how to assess risk, talk to parents, and refer for delabeling. You’ll also learn what happens in the allergy clinic, why the label matters, and how to be a better antimicrobial steward.

Learning Objectives

1. Describe the mechanisms and clinical manifestations of immediate and delayed hypersensitivity reactions to penicillin, including diagnostic criteria and risk stratification tools such as the PEN-FAST score.
2. Differentiate between low-, moderate-, and high-risk penicillin allergy histories in pediatric patients and identify appropriate candidates for direct oral challenge or allergy referral based on current evidence and guidelines.
3. Formulate an evidence-based approach for evaluating and counseling families in the Emergency Department about reported penicillin allergies, including when to recommend outpatient referral for formal delabeling.

Connect with Brad Sobolewski

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References

Khan DA, Banerji A, Blumenthal KG, et al. Drug Allergy: A 2022 Practice Parameter Update. J Allergy Clin Immunol. 2022;150(6):1333-1393. doi:10.1016/j.jaci.2022.08.028

Moral L, Toral T, Muñoz C, et al. Direct Oral Challenge for Immediate and Non-Immediate Beta-Lactam Allergy in Children. Pediatr Allergy Immunol. 2024;35(3):e14096. doi:10.1111/pai.14096

Castells M, Khan DA, Phillips EJ. Penicillin Allergy. N Engl J Med. 2019;381(24):2338-2351. doi:10.1056/NEJMra1807761

Shenoy ES, Macy E, Rowe T, Blumenthal KG. Evaluation and Management of Penicillin Allergy: A Review.JAMA. 2019;321(2):188–199. doi:10.1001/jama.2018.19283

Transcript

Note: This transcript was partially completed with the use of the Descript AI and the Chat GPT 5 AI

 Welcome to PEM Currents, the Pediatric Emergency Medicine podcast. As always, I'm your host, Brad Sobolewski, and today we are taking on a label that's misleading, persistent. Far too common penicillin allergy, it's often based on incomplete or inaccurate information, and it may end up limiting safe and effective treatment, especially for the kids that we see in the emergency department.

I think you've all seen a patient where you're like. I don't think this kid's really allergic to amoxicillin, but what do you do about it? In this episode, we're gonna break down the evidence, walk through what actually happens during de labeling and dedicated allergy clinics. Highlight some validated tools like the pen FAST score, which I'd never heard of before.

Preparing for this episode and discuss the current and future role of ED based penicillin allergy testing. Okay, so about 10% of patients carry a penicillin allergy label, but more than 90% are not truly allergic. And this label can be really problematic in kids. It limits first line treatment choices like amoxicillin, otitis media, or penicillin for strep throat, and instead.

Kids get prescribed second line agents that are less effective, broader spectrum, maybe more toxic or poorly tolerated and associated with a higher risk of antimicrobial resistance. So it's not just an EMR checkbox, it's a label with some real clinical consequences. And it's one, we have a role in removing.

And so let's understand what allergy really means. And most patients with a reported penicillin allergy, especially kids, aren't true allergies in the immunologic sense. Common misinterpretations include a delayed rash, a maculopapular, or viral exum, or benign, delayed hypersensitivity, side effects, nausea, vomiting, and diarrhea.

And unverified childhood reactions that are undocumented and nonspecific. Most of these are not true allergies. Only a very small subset of patients actually have IgE mediated hypersensitivity, such as urticaria, angioedema, wheezing, and anaphylaxis. These are super rare, and even then they may resolve over time without treatment.

If a parent or sibling has a history of a penicillin allergy, remember that patient might actually not be allergic, and that is certainly not a reason to label a child as allergic just because one of their first degree relatives has an allergy. So right now, in 2025, as I'm recording this episode, there are clinics like the Pats Clinic or the Penicillin Allergy Testing Services at Cincinnati Children's and in a lot of our peer institutions that are at the forefront of modern de labeling.

Their approach reflects the standard of care as outlined by the. Quad ai or the American Academy of Allergy, asthma and Immunology and supported by large trials like Palace. And you know, you have a great trial if you have a great acronym. So here's what happens step by step. So first you stratify the risk.

How likely is this to be a true allergy? And that's where a tool like the pen fast comes. And so pen fast scores, a decision rule developed to help assess the likelihood of a true penicillin allergy based on the patient's history. The pen in pen fast is whether or not the patient has a self-reported history of penicillin allergy.

They get two points if the reaction occurred in the past five years. Two points if the reaction is anaphylaxis or angioedema. One point if the reaction required treatment, and one point if the reaction was not due to testing. And so you can get a total score of. Up to six points. If you have a score of less than three.

This is a low risk patient and they can be eligible for direct oral challenge. A score greater than three means they're higher risk and they may require skin testing. First validation studies show that the PEN FFA score of less than three had a negative predictive value of 96.3%. Meaning a very, very low chance of a true allergy.

And this tool has been studied more extensively in adults, but pediatric specific adaptations are emerging, and they do inform current allergy clinic protocols. But I would not use this score in the emergency department just to give a kid a dose of amoxicillin. So. For low risk patients, a pen fast score of less than three or equivalent clinical judgment clinics proceed with direct oral challenge with no skin testing required.

The protocol is they administer one dose of oral amoxicillin and they observe for 62 120 minutes monitoring for signs of reaction Urticaria. Respiratory symptoms or GI upset. This approach is safe and effective. There was a trial called Palace back in 2022, which validated this in over 300 children. In adolescents.

There were no serious events that occurred. De labeling was successful in greater than 95% of patients. And skin tested added no benefit in low risk patients. So if the child tolerates this dose, then you can remove that allergy immediately from the chart. Parents and primary care doctors will receive a summary letter noting that the challenge was successful and that there's new guidance.

Children and families are told they can safely receive all penicillins going forward. And providers are encouraged to document this clearly in the allergy section of the EMR. So you're wondering, can we actually do this in the emergency department? Technically, yes, you can do what you want, but practically we're not quite there yet.

So we'd need clearer risk stratification tools like the Pen fast, a safe place for monitoring, post challenge, clinical pathways and documentation support. You know, a clear way to update EMR allergy labels across the board and involvement or allergy or infectious disease oversight. But it's pretty enticing, right?

See a kid you diagnose otitis media. You think that their penicillin allergy is wrong, you just give 'em a dose of amox and watch 'em for an hour. That seems like a pretty cool thing that we might be able to do. So some centers, especially in Canada and Australia, do have some protocols for ED or inpatient based de labeling, but they rely on that structured implementation.

So until then, our role in the pediatric emergency department is to identify low risk patients, avoid over document. Unconfirmed reactions and refer to allergy ideally to a clinic like the pets. So who should be referred and good candidates Include a child with a rash only, especially one that's remote over a year ago.

Isolated GI symptoms. Parents unsure of the details at all. No history of anaphylaxis wheezing her hives, and no recent serious cutaneous reactions. I would avoid referring and presume that this allergy is true. If they've had recent anaphylaxis, they've had something like Stevens Johnson syndrome dress, or toxic epidermolysis necrosis.

Fortunately, those are very, very rare with penicillins and there's a need for penicillin during the ED visit without allergy backup. So even though we don't have an ED based protocol yet. De labeling amoxicillin or penicillin allergy can start with good questions in the emergency department. So here's one way to talk to patients and families.

You can say, thanks for letting me know about the amoxicillin allergy. Can I ask you a few questions to better understand what happened? This is gonna help us decide the safest and most effective treatment for your child today, and then possibly go through a process to remove a label for this allergy that might not be accurate.

You wanna ask good, open-ended questions. What exactly happened when your child took penicillin or amoxicillin? You know, look for rash, hives, swelling, trouble breathing, or anaphylaxis. Many families just say, allergic, when the reaction was just GI upset, diarrhea or vomiting, which is not an allergy. How old was your child when this happened?

Reactions that occurred before age of three are more likely to be falsely attributed. How soon after taking the medicine did the reaction start? Less than one hour is an immediate reaction, but one hour to days later is delayed. Usually mild and probably not a true allergy. Did they have a fever, cold or virus at that time?

Viral rashes are often misattributed to antibiotics, and we shouldn't be treating viruses with antibiotics anyway, so get good at looking at ears and know what you're seeing. And have they taken similar antibiotics since then? Like. Different penicillins, Augmentin, or cephalexin. So if they said that they were allergic to amoxicillin, but then somehow tolerated Augmentin.

They're not allergic. If a patient had rash only, but no hive swelling or difficulty breathing, no reaction within the first hour. It occurred more than five years ago or before the kid was three. And especially if they tolerated beta-lactam antibiotics. Since then, they're a great candidate for de labeling and I would refer that kid to the allergy clinic.

Generally, they can get them in pretty darn quick. Alright, we're gonna wrap up this episode. Most kids labeled penicillin allergic or amoxicillin allergic, or not actually allergic to the medication. There are some scores like pen fasts that are validated tools to assess risk and support de labeling.

Direct oral challenge for most patients is safe, efficient, and increasingly the standard of care. There are allergy clinics like the Pats at Cincinnati Children's that can dela children in a single visit with oral challenges alone, needing no skin testing, and emergency departments can play a key role in identifying and referring these patients and possibly de labeling ourselves in the future.

Well, that's all for this episode on Penicillin Allergy. I hope you learn something new, especially how to assess whether an allergy label is real, how to ask the right questions and when to refer to an allergy testing clinic. If you have feedback, send it my way. Email, comment on the blog, a message on social media.

I always appreciate hearing from you all, and if you like this episode, please leave a review on your favorite podcast app. Really helps more people find the show and that's great 'cause I like to teach people stuff. Thanks for listening for PEM Currents, the Pediatric Emergency Medicine podcast. This has been Brad Sobolewski.

See you next time.