Safety and cost effectiveness of direct supervised ambulatory drug provocation tests in children with mild non-immediate reactions to beta-lactams

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 nonimmediate reactions. The work-up included sIgE, skin testing and drug provocation tests (DPTs) for immediate reactions and patch testing and DPTs for nonimmediate ones. Results Of the 510 included children, 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 nonimmediate 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 nonimmediate reactions, over half of which would also have been lost in a short DPT protocol. Selective responders to amoxicillin were more likely to have nonimmediate reactions, while clavulanic acid-selectivity was exclusive to the nonimmediate typology. Over half the cases with DPTs required 6-7 days of treatment for DHR confirmation.

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Diagnostic value and safety of penicillin skin tests in children with immediate penicillin allergy

Allergy and Asthma Proceedings ◽

10.2500/aap.2020.41.200082 ◽

2020 ◽

Vol 41 (6) ◽

pp. 442-448 ◽

Cited By ~ 1

Author(s):

Ilknur Kulhas Celik ◽

Irem Turgay Yagmur ◽

Ozge Yilmaz Topal ◽

Muge Toyran ◽

Ersoy Civelek ◽

...

Keyword(s):

Pediatric Patients ◽

Multivariate Logistic Regression Analysis ◽

Diagnostic Value ◽

Penicillin Allergy ◽

Skin Tests ◽

Provocation Tests ◽

Test Kit ◽

History Of ◽

Drug Provocation Tests ◽

Immediate Reactions

Background: The first-line method in the diagnosis of patients who describe an immediate reaction after penicillin intake is a skin test (ST) with penicillin reagents. Objectives: We aimed to determine the safety and diagnostic value of penicillin STs in the diagnosis of immediate reactions to penicillins in pediatric patients. Methods: The study included pediatric patients with suspected immediate reaction to penicillin who were subjected to STs by using a standard penicillin test kit as well as suspected penicillin and the drug provocation tests (DPT) with the suspected penicillin at our clinic. Results: A total of 191 patients (53.9% boys) with a median age of 6.83 years (interquartile range, 4.2‐12 years) were included in the study. The time from drug intake to the onset of reaction was ≤1 hour in 138 patients (72.3%) and 1 to 6 hours in 53 patients (27.7%). Penicillin allergy (PA) was confirmed by diagnostic tests in 36 of the 191 patients (18.8%). In multivariate logistic regression analysis, the history of both urticaria and angioedema (odds ratio [OR] 27.683 [95% confidence interval {CI}, 3.143‐243.837]; p = 0.003) and anaphylaxis (OR 56.246 [95% CI, 6.598‐479.489]; p < 0.001) were the main predictors of a PA diagnosis. Although ST results were positive in 23 patients (63.8%), 13 patients (26.2%) had positive DPT results despite negative ST results. The negative predictive value (NPV) of STs was calculated 92.2% (155/168). None of our patients experienced immediate or delayed systemic and/or local reactions in relation to the STs. Conclusion: A history of urticaria with angioedema and anaphylaxis were the main predictors of true PA in children with suspected immediate reactions. STs with penicillin reagents are safe for use in children. Although STs have a high NPV, DPT is the gold standard for diagnosis. DPTs should be performed as the final step of the diagnostic evaluation of PA in patients with negative ST results.

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Systemic reaction during intradermal skin tests with beta-lactams

BMJ Case Reports ◽

10.1136/bcr-2020-240050 ◽

2021 ◽

Vol 14 (3) ◽

pp. e240050

Author(s):

Joana Carvalho ◽

Georgeta Oliveira

Keyword(s):

Skin Testing ◽

Drug Hypersensitivity ◽

Systemic Reaction ◽

Skin Tests ◽

Beta Lactam ◽

Provocation Tests ◽

Maculopapular Eruption ◽

Intradermal Tests ◽

Amoxicillin Clavulanate ◽

Immediate Reactions

Beta-lactam (BL) antibiotics are the most frequent cause of drug hypersensitivity in children, inducing both immediate and non-immediate reactions. Here we report a case of a 4-year-old child with a disseminated maculopapular exanthema 7 days after the first dose of amoxicillin–clavulanate, referred to our paediatric allergy department. Skin prick tests were negative. Intradermal tests were performed and, after 10 hours, indurated wheals larger than 10×10 mm with progressive erythema and disseminated maculopapular eruption were developed, related to amoxicillin and amoxicillin–clavulanate. Systemic reactions to BL skin tests are rarely reported and the majority are immediate reactions. This case illustrates a rare example of a non-immediate systemic reaction to intradermal tests, underlying the importance of skin testing before drug provocation tests in cases of moderate to severe non-immediate reactions.

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