Don’t fear testing for, and delabeling, penicillin allergy


You are seeing a 28-year-old man for a same-day appointment. He has a history of opioid use disorder and chronic hepatitis C virus infection. He has been using injections of heroin and fentanyl for more than 6 years, and you can see in his medical record that he has had four outpatient appointments for cutaneous infections along with three emergency department visits for same in the past 2 years. His chief complaint today is pain over his left forearm for the past 3 days. He does not report fever or other constitutional symptoms.

Examination of the left forearm reveals 8 cm of erythema with induration and calor but no fluctuance. The area is moderately tender to palpation. He has no other abnormal findings on exam.

What’s your course of action?

Dr. Vega’s take

You want to treat this patient with antibiotics and close follow-up, and you note that he has a history of penicillin allergy. A note in his record states that he had a rash after receiving amoxicillin as a child.

Sometimes, we have to take the most expedient action in health care. But most of the time, we should do the right thing, even if it’s harder. I would gather more history of this reaction to penicillin and consider an oral challenge, hoping that the work that we put in to testing him for penicillin allergy pays dividends for him now and for years to come.

Penicillin allergy is very commonly listed in patient health records. In a retrospective analysis of the charts of 11,761 patients seen at a single U.S. urban outpatient system in 2012, 11.5% had documentation of penicillin allergy. Rash was the most common manifestation listed for allergy (37% of cases), followed by unknown symptoms (20%), hives (19%), swelling/angioedema (12%), and anaphylaxis (7%). Women were nearly twice as likely as men were to report a history of penicillin allergy, and patients of Asian descent had half the reported prevalence of penicillin allergy, compared with White patients.

Only 6% of the patients reporting penicillin allergy in this study had been referred to an allergy specialist. Given the consequences of true penicillin allergy, this rate is far too low. Patients with a history of penicillin allergy have higher risks for mortality from coexisting hematologic malignancies and penicillin-sensitive infections such as Staphylococcus species. They more frequently develop resistance to multiple antimicrobials and have longer average lengths of stay in the hospital.

Getting a good history for penicillin allergy can be challenging. Approximately three-quarters of penicillin allergies are diagnosed prior to age 3 years. Some children with a family history of penicillin allergy are mislabeled as having an active allergy, even though family history is not a significant contributor to penicillin allergy. Most rashes blamed on penicillin among children are actually not immunoglobulin (Ig) E–mediated and instead represent viral exanthems.

In response to these challenges, at the end of 2022, the American Academy of Allergy, Asthma & Immunology along with the American College of Allergy, Asthma and Immunology published new recommendations for the management of drug allergy. These recommendations provide an algorithm for the active reassessment of penicillin allergy. Like other recommendations in recent years, they call for a proactive approach in questioning the potential clinical consequences of the penicillin allergy listed in the health record.

First, the guidelines recommend against needing any testing for previous adverse reactions to penicillin, such as headache, nausea/vomiting, or diarrhea, that are not IgE-mediated. However, patients who have experienced these adverse reactions may still be reticent to take penicillin. For them and for adults with a history of mild to moderate reactions to penicillin more than 5 years ago, a single oral challenge test with amoxicillin is practical and can be used to exclude penicillin allergy.


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