When 'Allergic to Penicillin' Isn't True in Children

William T. Basco, Jr., MD, MS


November 01, 2017

Which 'Penicillin-Allergic' Children Have True Penicillin Allergy?

Previous studies have demonstrated that many patients who report that they have experienced a penicillin allergy reaction are not truly penicillin allergic.[1,2] Testing for penicillin allergy is a lengthy and complicated sequence. It first involves percutaneous skin testing, followed by subcutaneous injections, and finally an oral challenge. Therefore, many patients do not complete the testing and instead avoid penicillin and related drugs unnecessarily.

A recent study by Vyles and colleagues[3] identified children aged 3.5-18 years who presented to a single emergency department and whose parents reported that the child had a penicillin allergy. The investigators collected information on a 17-item questionnaire, obtaining details on the purported allergic reaction, including signs and symptoms experienced by the child and any family history of atopic illness. The goal was to identify a cohort of "low-risk" children who likely did not have true penicillin allergy and could therefore be tested for penicillin allergy.

Patients at high risk for penicillin allergy were eliminated. This included children whose reactions had respiratory or cardiovascular components, including wheezing, dyspnea, airway swelling, or blood pressure changes, and skin reactions (including diffuse erythema or bullous cutaneous reactions). Low-risk reactions were those that involved the skin (with or without itching), gastrointestinal symptoms (such as vomiting or diarrhea), and some upper respiratory symptoms (such as runny nose or cough). A child with only a family history of allergy was considered low-risk.

Families of the low-risk children were contacted after the emergency department visit to determine whether they would like to return for full-fledged penicillin testing. Children of families who agreed to testing went through the standard three-step testing sequence. The skin testing was considered positive if the wheal was ≥3 mm in diameter. A child with a positive skin test could proceed to a graduated oral challenge if no systemic symptoms were present.

Questionnaires were completed for 597 children. Most study children (72.6%) were classified as low-risk by the screening instrument, with 27.3% having at least one high-risk symptom. Most of the families of the low-risk children were interested in testing, and ultimately 100 children completed the full testing sequence.

The median age of the 100 children tested was 9 years; 60% were white, and 20% were African-American. Most previous diagnoses of penicillin allergy (92%) were made by a primary care physician, but only 14% of the reported reactions were actually witnessed by a medical provider. Rash (97%) and itching (63%) were the most commonly reported allergy symptoms; 17% of the 100 children tested had reported hives, 7% had diarrhea, 2% had nausea, and 2% had vomiting. Other symptoms were all present in ≤1% of the children.

Of the 100 children who went through the full testing protocol, 3 (3%) had a positive skin prick test. All (100%; 95% confidence interval, 96.4%-100%) were able to complete the oral challenge. The investigators concluded that the children who were classified as low-risk for true penicillin allergy based on the screening instrument had subsequent negative penicillin allergy test results.


I'll wager that this study codifies an approach that many physicians follow—assessing the risk for true penicillin allergy based on the history of symptoms and signs reported by patients and parents. This could be viewed as a pilot study. It outlines an approach and a tool to prospectively determine which children can safely be prescribed penicillin drugs. The investigators acknowledged that this is "not quite ready for primetime," and it is perhaps for that reason that they did not publish the survey tool as an appendix to the manuscript. Nonetheless, this study emphasizes the importance of detailed documentation and assessment of any potential allergic reaction in an effort to avoid misclassifying children as allergic in the first place.


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