Skin Tests Can Overestimate Penicillin Allergy

Ingrid Hein

November 14, 2019

Women are more likely to react to a skin prick test for penicillin allergy than men, investigators report.

"We don't really have any idea why," said Dayne Voelker, MD, from the Mayo Clinic in Rochester, Minnesota.

Initially, the researchers thought the data reflected the fact that women are more likely than men to engage with the healthcare system.

But after the data were adjusted, "we still showed women were more likely to be positive on a skin test than men," Voelker told Medscape Medical News.

"They may have different biomarkers or it may relate to estrogen. We don't honestly know," he explained.

"We may need more research to find out what's going on in the genome," he said at the American College of Allergy, Asthma & Immunology 2019 Annual Scientific Meeting in Houston, where he presented findings from the retrospective review.

Voelker and his colleagues looked at the electronic medical records of 30,883 patients at the Mayo Clinic who had undergone skin testing for penicillin allergy from January 2001 and December 2017, a period of 17 years.

They identified 20,658 female patients and 10,225 male patients who met that criterion.

Of the 329 patients who responded to skin prick testing with a wheal at least 3 mm by 3 mm, 298 were female and 31 were male (91% vs 9%).

Of the 170 patients who responded to skin prick testing with a wheal at least 5 mm by 5 mm, 122 were female and 48 were male (72% vs 28%).

Table. Women More Likely Than Men to Respond to Skin Prick Testing for Penicillin Allergy
Response Odds Ratio 95% Confidence Interval P Value
≥3×3 wheal 4.32 2.98–6.26 <.0001
≥5×5 wheal 2.54 1.82–3.56 <.0001

Not Clinically Relevant

However, if you look at the total responses to the 5×5 wheal — 122 of 20,658 women and 48 of 10,225 men — rates are not dissimilar between women and men (0.59% vs 0.47%), said Eric Macy, MD, from Kaiser Permanente in San Diego.

"This very large study confirms that women report penicillin allergy more commonly than men, but when tested using appropriate criteria, they are no more likely to be skin-test-positive than men," he told Medscape Medical News.

"We also know that women have more sensitive skin," he added. "If you use an inappropriately low criteria — a less than 5 mm wheal — women will respond with a positive result, but it's not clinically relevant."

This study is the largest series of penicillin skin test results ever reported, Macy pointed out, "and it tells us something very important: you cannot use the wrong criteria for skin testing."

We've been overcalling penicillin allergy by skin testing for a long time, he said. "From a public-health point of view, if you think people are allergic to penicillin — and up to 97% of them are not — you'll end up giving them antibiotics that will cause them more problems. We want to make sure they get the most narrow-spectrum antibiotic when it's indicated, and that often is penicillin."

"The key takeaway from this is that we need to always use at least a 5 mm wheal with flare greater than the wheal as the minimum criteria for a positive test result, as noted in the FDA-approved package insert for PrePen, the penicillin skin test antigen," said Macy. "If you use a wheal of 3 mm, it will give an invalid result."

In addition, skin testing for penicillin allergy should only be used to rule out those at high risk: patients with a history of anaphylaxis or the onset of acute hives within 1 hour of the first dose during the most recent course of penicillin, he said. "For the low-risk ones, you challenge them; you shouldn't bother skin testing anymore."

In a recent literature review that looked at the safety of penicillin allergy evaluation without skin testing, Macy and his colleagues conclude that direct oral amoxicillin challenges are safe, effective, and well tolerated.

"The current reference standard test to confirm the absence of a clinically significant immunologically mediated hypersensitivity to penicillin is tolerance of a therapeutic amoxicillin dose," Macy explained.

"A positive skin test does not define clinically significant penicillin allergy," he emphasized, pointing out that in this study, no oral challenges were performed to confirm penicillin tolerance.

American College of Allergy, Asthma & Immunology (ACAAI) 2019 Annual Scientific Meeting.

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