The Well-Entrenched Label of β-Lactam “Allergy”

What were you doing on September 28, 2022? Unless this was the anniversary of a significant event in your life, you probably cannot recall. A little known fact is that September 28 is National Penicillin Allergy Day. Their Web site (www.nationalpenicillinallergyday.com) asks, “Why is correctly identifying those who are not actually allergic to penicillin so important?” As a pharmacist who has to deal with issue on a regular basis, I agree that erroneous penicillin allergies are a major issue. Therefore, it was with interest that I read the article by Shaw and colleagues¹ that looked at utilizing pharmacy residents to review patients' β-lactam allergies with the goal of delabeling them from the medical record or clarifying their reaction.

Although I believe that Shaw and colleagues have made a valiant attempt to tackle this problem by utilizing the pharmacy residents at their institution, I feel that they have unfortunately come up short. Blame can surely be placed in part to patient's aging memories, multiple caregivers, duplicated charts at various providers, less than perfect medication allergy documentation by health care providers of all types, and human error.

Why do I feel that this study has come up short? For one, I find a bit of a disconnect between the author's Figure 1 and Figure 2. Figure 2 lists the 3 interview questions that were asked: What β-lactam agent did the patient react to? When did the reaction occur? How did the patient react? The authors state that, “Figure 2 illustrates the actions taken depending on the patient's response to the 3 interview questions.” Yet in Figure 2, when looking at patients who reported their β-lactam allergy more than 10 years ago, the next step is to administer the β-lactam if there is an indication for it and then to delabel the allergy if there is no reaction to it. Shaw and colleagues did not attempt to observe these patients receive a β-lactam and then delabel the allergy if no reaction. I have to give a disclaimer on my previous sentence, as Shaw and colleagues did not list what portion of their patients described their allergic reaction occurring more than 10 years ago.

Why does this more than 10-year-ago time frame concern me? Time does not cure all. Although Shaw and colleagues mention that patients can lose their sensitivity to immunoglobulin E–mediated β-lactam penicillin allergy after a decade, one cannot be sure that it is true without proper allergy testing. Sullivan and colleagues² showed a positive penicillin skin test of 22% after 10 years or more since apparent allergic reaction. Castells and colleagues³ state that less than 5% of patients labeled with a remote and low-risk history of penicillin allergy are found to be truly allergic after formal allergy testing. Shaw and colleagues planned for no allergy testing in their patients.

In my opinion, the greatest shortfall in this study was the lack of patient education. Pharmacists have been talking to patients about their medications for years, so I wonder why no further education was offered after it was decided that the patient's allergy met the criteria to be delisted? One could have explained to the patient why their symptoms were considered low risk. Patients who were hesitant to have their β-lactam allergy delisted might have felt more comfortable after hearing more information and having the opportunity to ask questions. Patients who still felt uncomfortable could also be referred to a provider for inpatient or later outpatient β-lactam allergy testing. In fact, the British Society for Allergy and Clinical Immunology has a recommendation for adults with low-risk symptoms that do not require allergy testing. These patients may still continue to avoid penicillin use if they do not have the reassurance of a negative allergy test, so testing should be considered in these patients.⁴ Lutfeali and colleagues⁵ utilized pharmacists to provide patient counseling at the time of negative penicillin allergy testing and again in 7 to 10 days, either via phone call or face-to-face visit. Of course, there is a cost to testing, but Macy and Shu⁶ found the cost-benefit ratio for penicillin allergy testing to be $1915 less per patient per year. With a reported incidence of 6% to 25% of the population, penicillin allergy is the most common drug allergy identified in patient's medical records.³ This equates to a potentially large savings nationwide.

I appreciate Shaw and colleagues' attempt to tackle this important issue, but I fear that it is indeed a heavy lift for a 3-month study led by pharmacy residents with a subsequent 90-day follow-up. It seems that the United Kingdom is on their way via the British Society for Allergy and Clinical Immunology guidelines to help provide a solution to this issue.⁴ In the United States, with so many providers and different electronic medical record systems that do not speak to each other, we have an uphill battle ahead. More multicenter, comprehensive studies with long-term follow-up are needed. If that happens, we will hopefully be able to open the National Penicillin Allergy Day Web site in the not too distant future, with the only reference being to the discovery of penicillin on September 28, 1928, by Alexander Fleming.⁷