Protocol-driven evaluation may improve drug allergy label accuracy

A study in Singapore has found 75-percent inaccuracy in drug allergy labels among patients, indicating the importance of drug allergy evaluation in verifying these labels.

“In a risk-stratified, protocolized setting, drug allergy evaluation is safe and the hypersensitivity reactions observed were mostly cutaneous in nature,” the researchers said. “Prolonged drug provocation testing, where indicated, increases the sensitivity of drug allergy evaluation and is important in the verification of allergy labels.”

This prospective study was conducted to examine the utility and safety of formal allergology evaluation, as well as to identify factors associated with accurate drug allergy labels. From March 2019 to June 2021, 331 patients (mean age 49 years, 37 percent male) who completed drug allergy evaluation to index drugs of concern were recruited.

The researchers recorded the baseline demographics, characteristics of index hypersensitivity reaction, and evaluation outcomes.

Overall, 170 beta-lactam antibiotics, 53 perioperative drugs, 43 others, 38 nonsteroidal anti-inflammatory drugs, and 27 nonbeta-lactam antibiotic evaluations were included. [Ann Acad Med Singap 2022;51:677-685]

Half of the patients (n=165, 50 percent) had an index reaction within 5 years, with latency of <4 hours in 125 (38 percent). Rash, angioedema, and urticaria were the most common index reactions. Based on multidisciplinary consensus, 57 (17 percent) evaluations were stratified as low risk, 222 (67 percent) moderate risk, and 52 (16 percent) high risk.

The researchers found allergy labels to be false (negative drug evaluation) in 3 out of 4 patients (n=248, 75 percent), while 16/237 patients (7 percent) skin tests, 44/331 (13 percent) in-clinic graded challenge, and 23/134 (17 percent) home prolonged challenges were positive (true drug allergy). Rash and urticaria were the most common evaluation reactions. No cases of anaphylaxis were recorded.

“Our study has shown that the majority of drug allergy labels are inaccurate. With formal allergological evaluations, more than 75 percent of drug allergy labels can be safely removed,” the researchers said.

“In addition, we have demonstrated the utility of prolonged drug challenges in allergy evaluation, particularly in individuals with nonimmediate reactions or reactions with unknown latency,” they noted.

Unfortunately, prolonged drug provocation is not consistently adopted even though it has been advocated to increase the sensitivity of drug allergy evaluation, especially in nonimmediate reactions occurring in adults. [J Allergy Clin Immunol Pract 2017;5:1394-1401]

“If the prolonged challenge were omitted, up to 23/83 (28 percent) of patients with true drug allergies would have been missed and their drug allergy labels erroneously removed based on our findings,” the researchers said.

“The rationale behind prolonged drug challenge lies in the fact that drug hypersensitivity reactions consist of both immediate and nonimmediate reactions (such as drug exanthems), with the latter requiring prolonged exposure to a drug before the allergic reaction occurs,” they explained.

Likewise, a longer drug exposure may be needed to draw the allergic response in drug allergy evaluation, according to the researchers.