Patterns of response and drugs involved in hypersensitivity reactions to beta‐lactams in children

Abstract

Background: Beta-lactams generate different allergenic determinants that induce selective or cross-reactive drug hypersensitivity reactions (DHRs). We aimed to identify the drugs involved, the selectivity of the response, the mechanism, and the value of the different diagnostic tests for establishing a diagnosis in children evaluated for DHRs to beta-lactams. Methods: Prospective study evaluating children aged under 16 years reporting DHRs to beta-lactams. Reactions were classified as immediate and non-immediate reactions. The workup included sIgE, skin testing, and drug provocation tests (DPTs) for immediate reactions and patch testing and DPTs for non-immediate ones.Results: Of the 510 children included, 133 were evaluated for immediate reactions and confirmed in 8.3%. Skin test/in vitro IgE contributed to diagnosing half of the cases. Selective reactions occurred with amoxicillin (63%), followed by common penicillin determinants (27%) and cephalosporins (0.9%).Among non-immediate reactions (11.4% of the 377 children evaluated), most required DPTs, 52.7% of which were positive at 6-7 days of drug challenge. Selective reactions were identified with amoxicillin (80%), penicillin G (7.5%), cephalosporins (7.5%), and clavulanic acid (5%). Urticaria and maculopapular exanthema were the most frequent entities.Conclusions: There were few confirmed cases of either type of reaction. Skin testing proved less valuable in non-immediate reactions, over half of which would also have been lost in a short DPT protocol. Selective responders to amoxicillin were more likely to have non-immediate reactions, while clavulanic acid selectivity was exclusive to the non-immediate typology. Over half the cases with DPTs required 6-7 days of treatment for DHR confirmation.

New perspectives on drug allergy in children

“…Selective responders to AX were more likely to have nonimmediate reactions, while CL selectivity was exclusive to the nonimmediate reactor group. 3 Nonclassic manifestations such as drug-induced enterocolitis syndrome (DIES) may also appear and are described in this issue. 4,5 The journal´s virtual issue on "Drug Allergy" includes several studies published recently addressing novel management of DHRs in children, focusing on in vivo and in vitro diagnostic tools, the role of hidden allergens, the importance of delabeling, and how to prevent future episodes through drug desensitization.…”

“…Indeed, Isabel Torres‐Rojas et al have analyzed the patterns of response of DHRs to β‐lactams in 530 children. Selective responders to AX were more likely to have nonimmediate reactions, while CL selectivity was exclusive to the nonimmediate reactor group 3 . Nonclassic manifestations such as drug‐induced enterocolitis syndrome (DIES) may also appear and are described in this issue 4,5 …”

Simplifying the drug provocation test in non‐immediate hypersensitivity reactions to amoxicillin in children: The experience of a tertiary care allergy unit

“…On the other hand, a prolonged DPT is questioned because of its impact on the gut microbiota and the potential risk of increasing antibiotic resistance. 1,3,[8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] So far there is no agreement on the best protocol to be used that reaches the best compromise between safety, time consumption, and potential side effects. Today it is a matter of debate the way of administering the first dose of antibiotic during the DPT, in particular, if it would be better to fraction or not the drug dose (calculated according to the bodyweight).…”

“…In addition, a prolonged DPT results in increased confidence in the future use of the same drug when compared with a single‐day DPT. On the other hand, a prolonged DPT is questioned because of its impact on the gut microbiota and the potential risk of increasing antibiotic resistance 1,3,8–24 . So far there is no agreement on the best protocol to be used that reaches the best compromise between safety, time consumption, and potential side effects.…”

Drug provocation tests in children: All that glitters is not gold

“…21 This question has been extensively analyzed by other authors and is not the focus of our study. [22][23][24][25][26][27][28][29] Rather, in this paper, we review the factors that may contribute to an incorrect interpretation of DPT resultsespecially focusing on the apparently positive ones-in the pediatric population, and which may have an impact on the positive predictive value of the test.…”