Mild to moderate hypersensitivity reactions to beta-lactams in children: a single-centre retrospective review

Abstract

ObjectiveBeta-lactam (BL) antibiotics are the most reported drugs in hypersensitivity reactions in children. More than 90% of these children tolerate the suspected drug after diagnostic work-up. Skin tests (STs) show low sensitivity. Our aim was to assess the performance of drug provocation tests (DPTs) without previous ST in mild and moderate delayed reactions and to propose a new DPT protocol.Design of the studyCharts from 213 children under 15 years of age referred for suspected BL allergy from 2011 to 1013 were reviewed. Prick, intradermal and patch tests were performed with major determinant penicilloyl-polylysine, minor determinant mixture, amoxicillin (AMX), cefuroxime, penicillin G and AMX–clavulamate. Children with negative skin tests underwent DPT. After an initial full dose of antibiotic, DPT was carried on for 3 days at home in patients reacting within the first 3 days of treatment. If the reaction took place from day 4 on of treatment, patients took the antibiotic for 5 days.ResultsWe included 108 girls and 105 boys. Mean age at the time of reaction was 3.66±3.06 years. 195 patients (91.5%) reacted to one BL. 154 reactions (67.2%) were non-immediate. Mild to moderate skin manifestations were most frequently reported. AMX–clavulanate was the most frequently involved (63.4%). DPT confirmed the diagnosis of drug hypersensitivity in 17 (7.3%) cases. These 17 patients had negative ST.ConclusionIn mild and moderate cases of BL hypersensitivity, diagnosis can be performed by DPT without previous ST

Towards a more precise diagnosis of hypersensitivity to beta‐lactams — an EAACI position paper

“…In studies that performed prolonged DPT, a rate of positive results ranging from 2% to 17.2% was found. Because such rate was >10% in several studies, it has been suggested that prolonged DPT increase the allergy workup sensitivity in nonimmediate reactors to BL.…”

“…DPT have been recommended by both the European guidelines 22,30,31,67,68 and the US practice parameter 35 as a part of the BL allergy workup. However, only the European guidelines 22,30,31,67,68 emphasized their role in the establishment of a firm diagnosis of During the last decade, DPT with the suspected BL have been performed in series larger than 100 subjects involving either pediatric [69][70][71][72][73][74][75][76][77][78][79][80][81][82][83][84][85][86] or adult 29,58,[87][88][89][90][91][92][93][94][95][96][97][98][99] populations or both, 18,100-109 highly enhancing our knowledge on the usefulness and safety of this diagnostic tool in BL allergy workup. This knowledge has contributed to achieving agreement on several areas of the general principles for DPT (high/strong) ( Table 5).…”

“…If a full dose is tolerated, a normal course of the drug can be administered. Nevertheless, according to some studies 77,84,86,95,97,98,103,107,108 (b) Some groups consider the tolerance of a MSUD or DTD enough to exclude a delayed hypersensitivity. 18,29,73,74,80,87,89,92,93,97,98,103,[106][107][108] In the related studies, 18,29,73,74,80,87,89,92,93,97,98,103,[106][107][108] the rate of positive responses to DPT with suspected BL ranged from 0% 29,89 to 7.7%.…”

“…18,29,73,74,80,87,89,92,93,97,98,103,[106][107][108] In the related studies, 18,29,73,74,80,87,89,92,93,97,98,103,[106][107][108] the rate of positive responses to DPT with suspected BL ranged from 0% 29,89 to 7.7%. 106 Other groups believe that a too short exposure to BL (in terms of days) can be responsible for false-negative DPT, this being the rationale for performing DPT with a duration of 2-5 days [69][70][71][75][76][77][78][79]82,83,85,86,95,99,104,105,…”

“…It should be noted that false negative results may also occur because of a too low dosage, missing cofactors like infections, and/or potential tolerance induction by the challenge procedure. 67 In studies that performed prolonged DPT, [69][70][71][75][76][77][78][79][81][82][83]85,86,88,90,95,99,104,105,109,111,112 a rate of positive results ranging from 2% 78 to 17.2% 90 was found. Because such rate was >10% in several studies, 69,70,88,90,95,105,111 it has been suggested that prolonged DPT increase the allergy workup sensitivity in nonimmediate reactors to BL.…”