Penicillin allergy delabelled in 90 percent of patients after evaluation

Research from Queen Mary Hospital in Hong Kong shows that 90 percent of patients with suspected penicillin allergy were delabelled after undergoing Prospective Assessment of Penicillin Allergy (PAPA), and one in six of them received penicillins safely ≥6 months later.

“In Hong Kong, the prevalence of reported beta-lactam and penicillin allergy among the general population and hospitalized patients is 2 and 5 percent, respectively, with >8,000 new physician-reported allergy labels generated every year. However, most penicillin allergy labels are found to be inaccurate after evaluation, which predisposes patients to a myriad of adverse clinical outcomes – including increased hospitalization, morbidity, mortality, [and also increased risk for] the emergence of multidrug-resistant organisms,” wrote the researchers. [World Allergy Organ J 2019;12:100048; JAMA Netw Open 2020;3:e204199; Hong Kong Med J 2021;27:192-197; J Hosp Infect 2020;106:35-42]

Adult patients (n=372; male, 35.2 percent; mean age, 59.4 years) referred for suspected penicillin allergy underwent PAPA between January 2020 and December 2021. [Asian Pac J Allergy Immunol 2025;43:10-17] Evaluation entailed comprehensive history taking with a focus on the timing of symptom onset of index reaction, which allowed stratification as immediate, nonimmediate and unknown types of reaction. Patients with suspected immediate reactions or uninformative histories were offered skin tests (ST), skin prick tests and intradermal tests (IDT), while patients with suspected nonimmediate reactions were offered delayed IDT. Choice of supplementary in vitro tests, such as basophil activation tests and lymphocyte transformation tests (LTT), could be added at evaluating allergist’s discretion. [Allergy 2016;71:1103-1134] If ST results were negative, patients would proceed to drug provocation tests (DPT).

“Out of 372 patients who completed PAPA, 90 percent were successfully delabelled. The remaining patients were diagnosed by positive ST [5 percent], DPT [5 percent] and LTT [0.3 percent],” reported the researchers. All patients with confirmed penicillin allergies by positive in vivo tests (ST or DPT) only showed minor reactions during workup, which were self-limiting and did not require any additional treatment other than oral antihistamines. No patients developed anaphylaxis or systemic reactions during evaluation.

“We did not identify any false-negative DPT or cases of resensitization, even among patients with history of severe immediate-type reactions,” highlighted the researchers. “This finding of a 100 percent negative predictive value [NPV] for DPT is in line with other studies that deemed direct oral challenge a safe and effective ‘gold-standard’ to delabel patients evaluated as low-risk for genuine allergies.” [Allergy Asthma Clin Immunol 2015;11:34; JAC Antimicrob Resist 2021;3:dlaa123]

During ≥6–12 months following delabelling or confirmation of allergy, 18 percent of delabelled patients received penicillins again and none of them reported any adverse reactions. Compared with patients with confirmed penicillin allergy who did not receive penicillins again, there was significantly less fluoroquinolone use among delabelled patients (30 vs 11 percent; p=0.004) during follow-up.

Overall NPV of penicillin skin testing was 95 percent, but was lower (88 percent) for patients with history of nonimmediate reactions. “To minimize the risk of a positive DPT, we advocate a more cautious approach towards counselling and investigation in patients with a history of severe nonimmediate reactions. In such cases, supplementary diagnostic tests such as complementary in vitro tests [eg, LTT or ELISpot] should be considered,” advised the researchers.