Patients should be retested for penicillin resensitization before being deemed nonallergic
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Patients with negative tests for penicillin allergy following initial reactions should be tested again later for resensitization, particularly when those reactions included anaphylaxis, according to a study published in Allergy.
Follow-up testing may prevent potentially severe reactions to subsequent prescriptions for these drugs, Inmaculada Doña, MD, PhD, of the allergy research group at Institute of Biomedical Research of Malaga, Spain, and colleagues wrote.
Study participants
The study involved 545 patients (67.5% women) with a clinical history of allergic reactions to penicillin and a median age of 34 years (interquartile range, 18-50) at the time of the reaction.
These cases included 296 (54.3%) immediate reactions, which occurred less than 6 hours after receiving the drug, and 249 (45.7%) nonimmediate reactions, which occurred more than 6 hours later.
Common symptoms in these reactions included urticaria or angioedema (60.9%), maculopapular exanthema (16.7%), anaphylaxis (15.2%), isolated respiratory symptoms (1.8%) and isolated gastrointestinal symptoms (0.4%). All the cases of anaphylaxis were immediate reactions.
Of the reactions, 71.9% were grade I, 15.5% were grade II and 12.5% were grade III, with no grade IV reactions reported.
Triggers included amoxicillin (56.1%), amoxicillin/clavulanic acid combinations (36%), penicillin (5.9%), ampicillin (0.5%) and piperacillin-tazobactam (0.2%).
Study results
When the researchers evaluated the patients 24 months (range, 12-72) after their last penicillin-induced reaction, they all had negative skin tests.
Next, the researchers randomly assigned the patients with grade I and II immediate reactions and all patients with nonimmediate reactions into two groups depending on whether they also had a drug provocation test (DPT; n = 306) or not (n = 239) with the culprit penicillin. All the patients who participated in a DPT tolerated the drug that was involved in their initial reaction.
When the researchers then retested patients with skin prick tests 34 days (range, 28-46) after the initial evaluation, there were 80 (14.7%) positive cases, with more of these cases occurring among patients who initially had immediate vs. nonimmediate reactions (21.3% vs. 6.8%; P < .0001).
Patients with positive retest results were older than those with negative retest results (P = .001). Also, patients with penicillin-induced anaphylaxis had higher rates of positive retests than patients with symptoms other than anaphylaxis (45.8% vs. 9.1%; P < .0001).
Logistic regression analysis showed patients experienced a greater risk for positive retests when they were conducted from the fifth week after the initial evaluation (OR = 4.64; 95% CI, 2.07-11.6), with risks increasing with the patient’s age as well (OR = 1.02; 95% CI, 1.01-1.04).
Patients with more severe immediate reactions had higher positive retesting rates, including 43.2% of those with grade III reactions and 47.8% of those with grade II reactions compared with 11.7% of those with grade I reactions (P < .0001).
Considering these findings, the researchers advised clinicians to retest patients when they have strong suspicions of allergic reactions despite negative testing before considering patients to be nonallergic, particularly when reactions are severe.
Perspective
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Penicillin allergy labels should be accurate because true penicillin allergy, which is rare, should be flagged so penicillin-based antibiotics are avoided appropriately and patients are not put at increased risk for a hypersensitivity reaction.
Also, penicillin allergy labels should be verified, because if patients will tolerate penicillins, then they are likely to have better cure rates, less costly care, less risk for adverse effects from second-line antibiotics and less risk for resistant organisms.
I am surprised by the percentages in the study showing resensitization to penicillin among patients with a history of anaphylaxis. Although we understand as allergists that the risk exists, this is higher than expected. These rates of resensitization are higher than I see in my practice, but it is known that penicillin reaction epidemiology differs between U.S. and European studies.
Patients with higher-risk histories could be considered for retesting. At the very least, we should educate patients at higher risk about red flags to look for if they are taking a penicillin-based antibiotic after negative testing.
I think a similar U.S. study would be interesting. Additionally, a study that did not perform skin testing but performed a challenge to evaluate for resensitization would also be interesting.
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