Montreal—When pharmacists are informed that children are allergic to amoxicillin, they might ask which test was used to confirm the allergy.

A study published online recently by JAMA Pediatrics reports that the skin tests most often used to predict allergies to amoxicillin are likely to be unreliable.

An investigation led by the Research Institute of the McGill University Health Centre (RI-MUHC) in Montreal emphasizes that an oral provocation or challenge test, with appropriate follow up, more efficiently and safely screens for nonlife-threatening reactions to amoxicillin in children.

“Our study suggests that skin tests are essentially useless as diagnostic tests, and that we should go directly to the graded provocation test that is highly sensitive and specific,” explained lead author Moshe Ben-Shoshan, MD, MSc, an allergist at the Montreal Children’s Hospital and an assistant professor of pediatrics at McGill University. “This is a game changer in the way physicians assess amoxicillin allergy in children given the fact that skin tests are still the recommended screening method in hospitals.”

With provocation or challenge (PC) tests, which are performed in hospitals or clinics where any serious reactions can be safely managed, the suspected allergen is gradually introduced to the patient. Background information in the article noted that as many as 10% of children develop rashes while taking antibiotics.

“The majority are diagnosed without further evaluation as allergic to the implicated antibiotic,” Ben-Shoshan said in an MUHC press release. “Most of the patients continue to avoid the suspect antibiotic in favor of alternatives which may be less effective, more toxic, and more expensive.”

The study, touted as the largest of its kind to assess the use of a graded PC in children who presented with a rash due to suspected amoxicillin allergy, focused on 818 children who presented to the MUHC Allergy clinic from March 2012 to April 2015.

Results indicate that 94.1% of the children, all of whom underwent the graded PC test, showed tolerance to amoxicillin. In fact, only 17 had an immediate positive reaction to amoxicillin, and only one within this group had a positive skin test. Another 31 had non-immediate reactions developing more than 1 hour after challenge; all were mild and manifested mainly as skin eruptions.

Study authors point out that skin tests can have a high false-negative rate for many antibiotics, including amoxicillin.

Of the 250 patients receiving annual follow-up, 55 received subsequent full treatment with amoxicillin, and 49 reported tolerance to the therapy. Another six developed nonimmediate cutaneous reactions.

History of a reaction occurring within 5 minutes of exposure was associated with immediate reactions to the PC, adjusted odds ratio of 9.6, while a rash that lasted longer than 7 days, adjusted odds ratio of 4.8, and parental history of drug allergy, adjusted odds ratio of 3.0, were associated with nonimmediate reactions to the PC, according to the report.

“Our study is the first to determine the percentage of immediate and non-immediate amoxicillin allergy in all children presenting with a suspected amoxicillin induced rash through a graded PC,” Ben-Shoshan noted. “Further, we showed that in children with a negative PC, amoxicillin can be safely used in the future, although under 10% may develop mild cutaneous symptoms upon subsequent exposure.'”

The researchers called for future studies to assess factors associated with specific PC outcomes, suggesting that specific association with genetic markers be investigated to accurately determine future risk for antibiotic allergic reactions.

In an accompanying commentary, John M. Kelso, MD, of the Scripps Clinic in San Diego, writes, “Given the morbidity and costs associated with being mislabeled as penicillin allergic, it is absolutely appropriate for children so labeled to be evaluated so that the majority who are not allergic can be ‘delabeled.’”

Kelso cautions, however, that the “chance of an anaphylactic reaction to an oral provocation challenge is small, but not 0, and anaphylaxis by definition is a potentially life-threatening event,” adding, “This emphasizes the importance of such challenges being performed in a medical setting with personnel and equipment able to recognize and treat anaphylaxis.”

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