Prior high-risk penicillin reactions should not prevent provocation challenges in children
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PHOENIX — Factors considered high risk for penicillin allergy should not preclude children from undergoing reevaluation, according to a study presented at the American Academy of Allergy, Asthma & Immunology Annual Meeting.
“Children with penicillin allergy labels should be referred to and evaluated by an allergist for potential delabeling, even if they had traditionally ‘high-risk’ histories of anaphylaxis, serum sickness-like reactions or prior positive penicillin allergy testing,” lead study author Susan S. Xie, MD, clinical fellow in the division of allergy and immunology at Cincinnati Children’s Hospital, told Healio.
Xie and colleagues reevaluated 1,553 risk-stratified children (median age at reaction, 1.8 years) listed in the penicillin allergy registry at Cincinnati Children's Hospital Medical Center to characterize higher risk vs. lower risk and determine which children should be eligible for drug provocation challenges and allergy delabeling.
“Large studies from multiple countries have already established tolerance rates of greater than 90% in children with penicillin-associated rashes when they are re-challenged to the culprit penicillin,” Xie said. “Our study found similar tolerance rates in children with higher-risk histories such as anaphylaxis and serum sickness-like reactions, who traditionally may have been excluded from referral or routine allergy testing.”
In all, 66.3% of children were categorized as having no risk, indicating they had an unknown family allergy history and had experienced a rash or hives more than 1 year before registry or other mild somatic symptoms; 27.3% were categorized as low risk, which included those who experienced a rash or hives within 1 year of registry, as well as swelling, difficulty breathing and reactions to all penicillins or cephalosporins; and 6.4% were categorized as high risk, indicating they had experienced serum sickness-like reactions, anaphylaxis, severe cutaneous reaction and prior positive penicillin skin testing or drug provocation challenges.
“We found that while only 31% of children classified as high-risk underwent challenges, 94% were tolerant. These nonallergic high-risk patients included 22 who originally had serum sickness-like reactions, three with anaphylaxis, four with prior positive skin testing and one with a prior allergic challenge. The two high-risk patients with allergic outcomes had histories of serum sickness-like reaction and possible anaphylaxis, but solely developed delayed-onset hives after their challenges,” Xie said.
“In comparison, patients classified as low risk and no risk in our registry were challenged at higher rates, 59% in both groups, and had similar tolerance rates of 92% in the low-risk group and 96% in the no-risk group,” Xie added.
Certain systemic symptoms likely deterred patients or providers from proceeding with challenges, Xie said. Specifically, patients with hand or foot swelling, vomiting or diarrhea, joint symptoms or fever were less likely to undergo drug challenges.
“However, children who experienced any systemic symptom still had a tolerance rate of 89% overall,” Xie said.
Future research will be aimed at guiding appropriate risk stratification of penicillin-allergic children, with the goal of being more inclusive with safely delabeling pediatric patients and preventing unnecessary avoidance of penicillin, Xie said.
“Given the small number of allergic outcomes even in reaction phenotypes deemed ‘high risk’ in children, we will continue to collect data in this population, and multicenter collaborations would be helpful,” Xie said.
Perspective
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Jumy (Olajumoke) Fadugba, MD, FAAAAI
This study was interesting because it sought to investigate a group of children with history of “high-risk” penicillin reactions; these are patients who are often not assessed. It was a retrospective study with the goal of identifying the characteristics of patients who underwent a direct oral challenge to penicillin (DPC) without a preceding skin test.
It was interesting to note that 32 “high-risk” patients did undergo DPC. However, as expected, fewer high-risk patients underwent DPC than those who had low-risk history.
The researchers found that most of the “high-risk” children (94%) did tolerate the DPC, a similar tolerance rate as those with low-risk history.
These are promising initial data, but further investigation of these “high-risk” patients would better guide how we should manage these patients. For example, some high-risk reactions (such as serum sickness, Stevens-Johnson syndrome and DRESS, or drug rash with eosinophilia and systemic symptoms) require several days of antibiotic use before they manifest; therefore, one could consider several days of an oral challenge to really determine whether there is tolerance.
In addition, it is possible that the providers felt that the challenged high-risk patients were more likely to tolerate DPC than the nonchallenged high-risk patients. A future goal might be a prospective study that identifies specific high-risk categories of patients who will undergo DPC in order to determine outcome.
Overall, this study should encourage providers to not simply dismiss patients with “high-risk” histories, but rather to probe histories further and, if appropriate, administer DPC.
Chief, section of allergy & immunology
Fellowship program director of allergy & immunology
Perelman School of Medicine, University of Pennsylvania
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Xie SS, et al. Abstract 185. Presented at: AAAAI Annual Meeting; Feb. 25-28, 2022; Phoenix (hybrid meeting).
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