Beta-lactam hypersensitivity stays baffling

Approximately 75% of skin test results in people with allergic reactions to beta-lactams were negative, based on data from 175 patients.

The World Allergy Organization differentiates between allergic and non-allergic hypersensitivity, which can be useful in advising patients with drug hypersensitivity reactions (DHR), wrote Dr. Lukas Jörg from the University Hospital Zurich, Switzerland, and colleagues. “In an allergy to beta-lactam antibiotics (BL), the chemical structure plays a key role,” they write.

The current diagnostic approach for suspected allergic DHR is largely based on medical history, clinical symptoms, skin tests, in vitro tests, and drug provocation tests, the researchers noted. Although skin tests are effective for immediate reactions, their negative predictive value has shown lower reliability for delayed DHR, and “extrapolation of predictive values ​​to a population with a different prevalence of drug allergy may lead to incorrect conclusions,” the researchers said.

To determine the value of positive skin tests in predicting beta-lactam allergies, the researchers conducted a cross-sectional study of 175 people who had a history of DHR to a penicillin or cephalosporin antibiotic and who were investigating on two University centers have been referred. Of these, 152 suspected DHR against penicillins and 23 against cephalosporins. The mean age of the patients was 47 years, 63% were female. 71 patients had a maculopapular rash, 45 showed an immediate DHR reaction.

In the study published in the World Allergy Organization Journal, a total of 44 patients (25.1%) had positive skin tests, including 37% of patients with immediate DHR and 20.0% of patients with delayed DHR. The positivity of the skin prick or intradermal test (IDT) decreased over time from 47.8% to 23.5% with immediate DHR and from 23.0% to 12.9% with delayed DHR after 3 years .

Patients with more severe forms of delayed DHR had a higher proportion of positive skin test results, with the highest rates in patients with macular rash (20.9%), drug reactions with eosinophilia and systemic symptoms (DRESS; 75%), and both pustular and bullous rash (50%) for both). However, no sensitization was seen in patients with delayed urticaria or unspecified delayed rash, the researchers noted.

Positive skin test results were also more common in patients with a shorter latency to onset of symptoms after drug exposure; 29.5% for 0 – 3 days vs 11.6% for more than 3 days.

Skin tests for areas outside the infested area were negative. Although a combination of patch test and IDT produced an additional positive result in 2/77 patients, further in vitro tests reduced the total proportion of negative test results from 75% to 72%.

“Overall, we were unable to make a final diagnosis in 27/45 patients, even including additional in-vitro tests,” the researchers write in their discussion of the results. They hypothesized that skin test results in patients with delayed responses could be improved if performed in areas affected by the index response, which gave positive results 31% of the time, compared to no positive results from tests in areas outside the index range. “This difference may be due to what is believed to be a more pronounced index response with spread to the forearms (a common test area for IDT),” they said. “However, this could suggest that the sensitivity of these tests could be improved if performed on areas of skin affected by the index reaction,” they added.

In the study, researchers admitted that they usually couldn’t distinguish the reasons for negative test results. “If you have a history of moderate or severe reactions, we therefore recommend not only avoiding the triggering agent, but also avoiding potentially cross-reactive beta-lactams (as in skin test-positive patients),” they said. However, the team had a larger longitudinal study “with defined recommendations to avoid or

Study results were limited by several factors, including the relatively small study population, a short follow-up time, and a potential overestimation of skin test positivity, the researchers noted.

“A larger patient cohort and a longer observation period of these study patients with systematic drug exposure assessment could improve recommendations, especially among those with negative test results,” they said.

The results suggest that drug provocation tests may be appropriate for immediate DHR, but may be unnecessary in patients with delayed DHR, they concluded.

Confirmation of allergies improves care

“We are at a point where it is very important to understand beta-lactam antibiotic allergies because they are such a large number of antibiotics and the workhorses of many of our first-line infection treatments,” said Kimberly G. Blumenthal , MD, MSc, from Massachusetts General Hospital, Boston, in an interview with Medscape Medical News. “Beta-lactams include penicillins and cephalosporins and are the most commonly reported drug allergies. It is therefore important to know who is or is not really allergic, as choosing alternatives to these drugs can be harmful.

The current study results confirm much of the published data, although it is important for different countries to self-assess their own epidemiology for confirmed allergies, added Blumenthal. The current study, conducted in Switzerland, uses “more extensive tests than those we use in the United States,” including blood tests, skin tests, and patch tests. The results add to the collective knowledge of the value of these tests, she said.

Blumenthal highlighted the researchers’ table of late-read skin test results in patients with delayed drug hypersensitivity reactions. The table is useful for seeing what value the tests had in evaluating researchers, she said. For example, the study population only had four cases of DRESS, but three of those had a positive patch test. While this is a small number, it suggests a possible value when doing some testing that is not routinely done in the United States.

Overall, the study highlights the need for more staff training to conduct more comprehensive drug allergy testing, Blumenthal said. More tests to confirm allergies can help a proper diagnosis and affect care, and even if testing is less extensive in the United States than elsewhere, “there are some beta-lactam allergy tests that could be done in primary care” and in other environments, she says noted.

World Allergy Organ J. Published online November 5, 2021. Full text

The study was funded by the Ulrich-Mueller-Gierok Allergy Foundation, Bern, Switzerland, and CK-Care (Christine Kühne – Center for Allergy Research and Education), Davos, Switzerland. The researchers and Blumenthal did not disclose any relevant financial relationships.

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