Penicillin Allergy in Children Substantially Overreported

Nicola M. Parry, DVM

July 03, 2017

Most children with parent-reported symptoms of penicillin allergy have negative results for a true allergic reaction to the drug, a new study shows.

David Vyles, DO, from the Medical College of Wisconsin, Milwaukee, and colleagues published the results of their study online July 3 in Pediatrics.

Among children categorized as low risk for penicillin allergy on the basis of a pediatric emergency department (ED) questionnaire, all tested negative for true penicillin allergy.

"Our results showed that the majority of children had rash and itching as their primary reported symptom of allergy," the authors write. "Consistent with our hypothesis, all children with symptoms deemed to be low risk for true [immunoglobulin E (IgE)]-mediated drug hypersensitivity ultimately had negative results for true penicillin allergy after the standard 3-tier testing process."

Penicillin allergy is the most frequently reported drug allergy, and its reporting affects how clinicians treat affected patients.

According to the authors, although many children present to the pediatric ED with parent-reported symptoms of penicillin allergy, most of these symptoms are low risk for true reaction.

However, because clinicians in the pediatric ED cannot safely and quickly diagnose true penicillin allergy, they avoid giving penicillin to children with a reported penicillin allergy. Thus, many children are not receiving optimal antibiotic treatment because of penicillin allergy misdiagnosis.

The gold standard for diagnosing penicillin allergy comprises a three-tier testing process, in which a percutaneous skin test is followed by more sensitive intracutaneous testing and an oral drug challenge. But this process is time-consuming and may be painful, the authors say.

The researchers therefore aimed to determine whether a risk-stratification allergy questionnaire could identify a low-risk population of children who could tolerate penicillin without an IgE-mediated allergic reaction. They used the standard three-tier testing process to check for penicillin allergy in children identified as low risk based on information reported in the questionnaire.

They hypothesized that children who presented to the pediatric ED with low-risk symptoms of allergy would test negative for true IgE-mediated penicillin hypersensitivity.

The researchers administered the penicillin allergy questionnaire to parents who presented their children to an urban pediatric ED and reported symptoms of penicillin allergy in the children. The questionnaire covered a range of questions, including the age at which the child's allergy was diagnosed, what antibiotic the child was taking at the time of diagnosis, the indication for the antibiotic treatment, and what allergy symptoms the child experienced.

The study included questionnaires from parents of 597 children aged between 3.5 and 18 years, and the researchers used the answers provided by the parents to help categorize the risk level for true penicillin allergy in each child.

The researchers categorized reported reactions as low risk if they were unlikely to involve a severe Ig-E mediated reaction or a T-cell-driven process. In contrast, they categorized reactions as high risk if they were likely IgE-mediated (such as respiratory or cardiovascular symptoms) or T-cell-driven (such as bullous cutaneous reaction), and thus represented a high clinical risk for further reactions to penicillin.

According to the authors, 434 (72.6%) children had low-risk symptoms of allergy to penicillin, and 163 (27.3%) had at least one high-risk symptom of allergy.

Of the children with low-risk symptoms of allergy, 352 (81.1%) of parents wanted to pursue penicillin allergy testing. Overall, based on eligibility and family availability, 100 (33.1%) of the low-risk children underwent allergy testing.

The most commonly reported allergy symptoms were rash (97%) and itching (63%). In 92% of cases, the parents noted that their primary care physician had diagnosed the allergy. The researchers contacted all 100 primary care physicians to confirm the allergy symptoms in these children, and found that a clinician had witnessed the allergic reaction in only 14 children; the remaining cases involved only parent-reported symptoms.

The researchers also found that all 100 children (100%; 95% confidence interval, 96.4% - 100%) had negative results for penicillin allergy after oral challenge. Of those tested, only three children had positive results on percutaneous testing, and all three passed a subsequent oral drug challenge.

Dr Vyles and colleagues thus stress that low-risk symptoms of parent-reported penicillin allergy in the pediatric ED probably do not correspond to true allergy to the drug.

Because the questionnaire also successfully identified children at low risk for penicillin allergy, the authors highlight its potential as a safe alternative to time-consuming, expensive, and labor-intensive penicillin skin testing in the ED.

"Utilization of this questionnaire in the pediatric ED may facilitate increased use of first-line penicillin antibiotics," they conclude.

This study was supported by grants from the American Academy of Pediatrics and a Children's Hospital of Wisconsin Foundation Vice Innovation award. The authors have disclosed no relevant financial relationships.

Pediatrics. Published online July 3, 2017.

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