Prospective study of 5-day challenge with penicillins in children

Birgitte Tusgaard Petersen, Josefine Gradman, Birgitte Tusgaard Petersen, Josefine Gradman

Abstract

Objectives: To examine if a 5-day challenge with penicillin improves the diagnostic sensitivity compared with a single full dose in children with mild skin reactions.

Design: Subjects referred with suspected allergy to penicillin were consecutively included. Irrespectively of the morphology of the index reaction and the result of specific IgE, all subjects underwent a two-step titrated drug provocation test (DPT) with the culprit drug followed by a 5-day challenge at home.

Participants: Children and adolescents aged 0-18 years referred to allergic workup for penicillin hypersensitivity at two paediatric Danish centres. Only subjects with non-severe skin reactions were included.

Results: A total of 305 subjects were included and 22 (7%) of the DPTs were positive. Three subjects reacted within 1 hour of the first full dose and nine reacted 1-8 hours after the first full dose. Additional 10 positive reactions were observed during the prolonged provocation. Seven subjects reacted after the second full dose and three reacted after 3-6 days. Only mild skin rashes were observed. Eighteen subjects had a specific IgE to a penicillin >0.1 kU/L. Only one of these had a positive DPT.

Conclusion: In children, a DPT with penicillins should include at least two full doses. In children with mild hypersensitivity reactions it may be safe to perform DPTs despite a low specific IgE.

Trial registration number: NCT04331522.

Keywords: history of medicine; pharmacology.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
A schematic illustration of the drug provocation test. t.i.d, three times a day.
Figure 2
Figure 2
The time interval from first full dose to the appearance of a reaction and the morphology of the rash.

References

    1. Erkoçoğlu M, Kaya A, Civelek E, et al. . Prevalence of confirmed immediate type drug hypersensitivity reactions among school children. Pediatr Allergy Immunol 2013;24:160–7. 10.1111/pai.12047
    1. Rebelo Gomes E, Fonseca J, Araujo L, et al. . Drug allergy claims in children: from self-reporting to confirmed diagnosis. Clin Exp Allergy 2008;38:191–8. 10.1111/j.1365-2222.2007.02870.x
    1. Castells M, Khan DA, Phillips EJ. Penicillin allergy. N Engl J Med 2019;381:2338–51. 10.1056/NEJMra1807761
    1. Torres MJ, Celik GE, Whitaker P, et al. . A EAACI drug allergy interest group survey on how European allergy specialists deal with β-lactam allergy. Allergy 2019;74:1052–62. 10.1111/all.13721
    1. Torres MJ, Blanca M, Fernandez J, et al. . Diagnosis of immediate allergic reactions to beta-lactam antibiotics. Allergy 2003;58:961–72. 10.1034/j.1398-9995.2003.00280.x
    1. Romano A, Blanca M, Torres MJ, et al. . Diagnosis of nonimmediate reactions to beta-lactam antibiotics. Allergy 2004;59:1153–60. 10.1111/j.1398-9995.2004.00678.x
    1. Blanca M, Romano A, Torres MJ, et al. . Update on the evaluation of hypersensitivity reactions to betalactams. Allergy 2009;64:183–93. 10.1111/j.1398-9995.2008.01924.x
    1. Romano A, Atanaskovic-Markovic M, Barbaud A, et al. . Towards a more precise diagnosis of hypersensitivity to beta-lactams - an EAACI position paper. Allergy 2020;75:1300–15. 10.1111/all.14122
    1. Summaries of product characteristics, 2020. Available:
    1. Mori F, Cianferoni A, Barni S, et al. . Amoxicillin allergy in children: five-day drug provocation test in the diagnosis of nonimmediate reactions. J Allergy Clin Immunol Pract 2015;3:375–80. 10.1016/j.jaip.2014.11.001
    1. Fransson S, Mosbech H, Kappel M, et al. . The Importance of Prolonged Provocation in Drug Allergy - Results From a Danish Allergy Clinic. J Allergy Clin Immunol Pract 2017;5:1394–401. 10.1016/j.jaip.2017.02.024
    1. Ratzon R, Reshef A, Efrati O, et al. . Impact of an extended challenge on the effectiveness of β-lactam hypersensitivity investigation. Ann Allergy Asthma Immunol 2016;116:329–33. 10.1016/j.anai.2016.01.018
    1. Labrosse R, Paradis L, Lacombe-Barrios J, et al. . Efficacy and safety of 5-day challenge for the evaluation of nonsevere amoxicillin allergy in children. J Allergy Clin Immunol Pract 2018;6:1673–80. 10.1016/j.jaip.2018.01.030
    1. Blanca-López N, Zapatero L, Alonso E, et al. . Skin testing and drug provocation in the diagnosis of nonimmediate reactions to aminopenicillins in children. Allergy 2009;64:229–33. 10.1111/j.1398-9995.2008.01903.x
    1. Confino-Cohen R, Rosman Y, Meir-Shafrir K, et al. . Oral challenge without skin testing safely excludes clinically significant delayed-onset penicillin hypersensitivity. J Allergy Clin Immunol Pract 2017;5:669–75. 10.1016/j.jaip.2017.02.023
    1. Kuruvilla M, Shih J, Patel K, et al. . Direct oral amoxicillin challenge without preliminary skin testing in adult patients with allergy and at low risk with reported penicillin allergy. Allergy Asthma Proc 2019;40:57–61. 10.2500/aap.2019.40.4184
    1. Mustafa SS, Conn K, Ramsey A. Comparing direct challenge to penicillin skin testing for the outpatient evaluation of penicillin allergy: a randomized controlled trial. J Allergy Clin Immunol Pract 2019;7:2163–70. 10.1016/j.jaip.2019.05.037
    1. Wong T, Atkinson A, t'Jong G, et al. . Beta-lactam allergy in the paediatric population. Paediatr Child Health 2020;25:62–3. 10.1093/pch/pxz179
    1. Jaoui A, Delalande D, Siouti S, et al. . Safety and cost effectiveness of supervised ambulatory drug provocation tests in children with mild non-immediate reactions to beta-lactams. Allergy 2019;74:2482–4. 10.1111/all.13871
    1. Gomes ER, Brockow K, Kuyucu S, et al. . Drug hypersensitivity in children: report from the pediatric Task force of the EAACI drug allergy interest group. Allergy 2016;71:149–61. 10.1111/all.12774
    1. van der Poorten M-LM, Van Gasse AL, Hagendorens MM, et al. . Serum specific IgE antibodies in immediate drug hypersensitivity. Clin Chim Acta 2020;504:119–24. 10.1016/j.cca.2020.02.005
    1. Fernández TD, Torres MJ, Blanca-López N, et al. . Negativization rates of IgE radioimmunoassay and basophil activation test in immediate reactions to penicillins. Allergy 2009;64:242–8. 10.1111/j.1398-9995.2008.01713.x
    1. Tonson la Tour A, Michelet M, Eigenmann PA, et al. . Natural history of benign Nonimmediate allergy to beta-lactams in children: a prospective study in Retreated patients after a positive and a negative provocation test. J Allergy Clin Immunol Pract 2018;6:1321–6. 10.1016/j.jaip.2017.10.008
    1. Solensky R, Earl HS, Gruchalla RS. Lack of penicillin resensitization in patients with a history of penicillin allergy after receiving repeated penicillin courses. Arch Intern Med 2002;162:822–6. 10.1001/archinte.162.7.822

Source: PubMed

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