Safety of direct oral provocation test to delabel reported mild beta-lactam allergy in infants
Main Article Content
Keywords
Beta-Lactam Allergy, Drug Hypersensitivity, Drug Provocation Test, Infants
Abstract
Background: Around 10% of people report a drug allergy and avoid some medications because of fear of allergic reactions. However, only after a proper diagnostic workup can some of these reactions be confirmed as allergic or nonallergic hypersensitivities. Beta-lactams (BLs) are the most common medication suspected of being involved in drug hypersensivity reactions (DHRs) in children. Recently, direct oral provocation tests (DPT) with BLs gained popularity within pediatric populations as a tool for delabeling children with suspected BL allergies. This study aimed to evaluate the safety of direct provocation tests in infants with mild cutaneous non-immediate reactions to BLs.
Methods: The authors retrospectively analyzed the data of 151 infants between 2015 and 2022, referred for evaluating a suspected allergy to BLs that occurred before age 24 months.
Results: The mean age of the children, including 55% male kids, at the suspected reaction was 15.9 months and the mean age at the time of the DPT was 39.6 months. In most cases, antibiotics were prescribed to treat common upper respiratory infections, such as acute otitis (54.3%) and acute tonsillitis (27.2%). Amoxicillin was considered the culprit drug in 62.9% of the cases, and the combination of amoxicillin–clavulanic acid in the case of 33.8% of children. The most frequent associated cutaneous clinical manifestations were maculopapular exanthema in 74.8% and delayed urticaria/angioedema in 25.2%. Of the 151 infants evaluated, parents of 149 infants agreed for a direct DPT, and only three had a positive test (2%). Symptoms resulting from the DPT were mild and easily treatable.
Conclusions: A direct DPT without prior tests is a safe and effective procedure to delabel BL allergy, even in infants. The authors wish to emphasize the importance of properly validating BL allergy suspicions by promoting appropriate diagnostic procedures in infants as, in most cases, DHRs can be excluded and there is no need for further therapeutic restrictions.
References
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14. Bousquet P-J, Gaeta F, Bousquet-Rouanet L, Lefrant J-Y, Demoly P, Romano A. Provocation tests in diagnosing drug hypersensitivity. Curr Pharm Design. 2008;14(27):2792-802. 10.2174/138161208786369731
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20. Iammatteo M, Alvarez Arango S, Ferastraoaru D, Akbar N, Lee AY, Cohen HW, et al. Safety and outcomes of oral graded challenges to amoxicillin without prior skin testing. J Allergy Clin Immunol Pract. 2019;7(1):236–43. 10.1016/j.jaip.2018.05.008
21. Felix MMR, Kuschnir FC. Direct oral provocation test is safe and effective in diagnosing beta-lactam allergy in low-risk children with mild cutaneous reactions. Front Pharmacol. 2020 Aug 7;11:1223. 10.3389/fphar.2020.01223
22. Zambonino MA, Corzo JL, Muñoz C, Requena G, Ariza A, Mayorga C, et al. Diagnostic evaluation of hypersensitivity reactions to beta-lactam antibiotics in a large population of children. Pediat Allergy Immunol. 2014;25(1):80–7. 10.1111/pai.1215
23. Mirakian R, Leech SC, Krishna MT, Richter AG, Huber PAJ, Farooque S, et al. Management of allergy to penicillins and other beta-lactams. Clin Exp Allergy. 2015;45(2):300–27. 10.1111/cea.12468
24. Böhm R, Proksch E, Schwarz T, Cascorbi I. Drug hypersensitivity—-Diagnosis, genetics and prevention. Dtsch Arztebl Int. 2018;115:501–12. 10.3238/arztebl.2018.0501
25. Mill C, Primeau MN, Medoff E, Lejtenyi C, Keefe AO, Netchiporouk E, et al. Assessing the diagnostic properties of a graded oral provocation challenge for the diagnosis of immediate and non-immediate reactions to amoxicillin in children. JAMA Pediatr. 2016;170(6):e160033. 10.1001/jamapediatrics.2016.0033
26. Exius R, Gabrielli S, Abrams EM, O’Keefe A, Protudjer JLP, Lavine E, et al. Establishing amoxicillin allergy in children through direct graded oral challenge (GOC): Evaluating risk factors for positive challenges, safety, and risk of cross-reactivity to cephalosporines. J Allergy Clin Immunol Pract. 2021;9(11):4060–66. 10.1016/j.jaip.2021.06.057
27. Prieto A, Muñoz C, Bogas G, Fernández-Santamaría R, Palomares F, Mayorga C, et al. Single-dose prolonged drug provocation test, without previous skin testing, is safe for diagnosing children with mild non-immediate reactions to beta-lactams. Allergy Eur J Allergy Clin Immunol. 2021;76(8):2544–54. 10.1111/all.14800
28. Kuniyoshi Y, Tsujimoto Y, Banno M, Taito S, Ariie T, Kubota T, et al. Beta-lactam allergy and drug challenge test in children: A systematic review and meta-analysis. Pediat Res. 2023;93(1):22–30. 10.1038/s41390-022-02076-x
29. Srisuwatchari W, Phinyo P, Chiriac AM, Saokaew S, Kulalert P. The safety of the direct drug provocation test in beta lactam hypersensitivity in children: A systematic review and meta-analysis. J Allergy Clin Immunol Pract. 2023;11(2):506–18. 10.1016/j.jaip.2022.11.035
30. Lee CE, Zembower TR, Fotis MA, Postelnick MJ, Greenberger PA, Peterson LR, et al. The incidence of antimicrobial allergies in hospitalized patients: Implications regarding prescribing patterns and emerging bacterial resistance. Arch Intern Med. 2000 Oct 9;160(18):2819–22. 10.1001/archinte.160.18.2819
31. Koosakulchai V, Sangsupawanich P, Wantanaset D, Jessadapakorn W, Jongvilaikasem P, Yuenyongviwat A. Safety of direct oral provocation testing using the-amoxicillin-2-step-challenge in children with history of non-immediate reactions to amoxicillin. World Allergy Organ J. 2021;14(7):100560. 10.1016/j.waojou.2021.100560
32. Arıkoğlu T, Kuyucu S, Caubet JC. New diagnostıc perspectives in the management of pediatrıc beta-lactam allergy. Pediat Allergy Immunol. 2022;33(3):e13745. 10.1111/pai.13745
33. Pongracic JA, Bock SA, Sicherer SH. Oral food challenge practices among allergists in the United States. J Allergy Clin Immunol. 2012;129(2):564–6. 10.1016/j.jaci.2011.09.024
34. Lezmi G, Alrowaishdi F, Bados-Albiero A, Scheinmann P, de Blic J, Ponvert C. Non-immediate-reading skin tests and prolonged challenges in non-immediate hypersensitivity to beta-lactams in children. Pediat Allergy Immunol. 2018;29(1):84–89. 10.1111/pai.12826
35. Romano A, Blanca M, Torres MJ, Bircher A, Aberer W, Brockow K, et al. Diagnosis of non-immediate reactions to β-lactam antibiotics. Allergy Eur J Allergy Clin Immunol. 2004;59(11):1153–60. 10.1111/j.1398-9995.2004.00678.x
36. Padial A, Antunez C, Blanca-Lopez N, Fernandez, TD, Cornejo-Garcia JA, Mayorga C, et al. Non-immediate reactions to β-lactams: Diagnostic value of skin testing and drug provocation test. Clin Exp Allergy. 2008;38(5):822–8. 10.1111/j.1365-2222.2008.02961.x
37. Kuruvilla M, Shih J, Patel K, Scanlon N. 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(1):57–61. 10.2500/aap.2019.40.4184
38. Atakul G, Köse SS, Atay O, Boyacioglu OK, Al S. Asilsoy S, et al. Oral challenge without penicillin skin tests in children with suspected beta-lactam hypersensitivity. J Child Sci. 2022;12(1):E133–7. 10.1055/s-0042-1757151
39. Chiriac AM, Demoly P. Drug provocation tests: Up-date and novel approaches. Allergy Asthma Clin Immunol. 2013;9(1):12. 10.1186/1710-1492-9-12
40. Torres MJ, Adkinson NF, Caubet JC, Khan DA, Kidon MI, Mendelson L, et al. Controversies in drug allergy: Beta-lactam hypersensitivity testing. J Allergy Clin Immunol Pract. 2019;7(1):40–45. 10.1016/j.jaip.2018.07.051
41. Kitsos N, Cassimos D, Trypsianis G, Xinias I, Roilides E, Grivea I, et al. Drug allergy evaluation in children with suspected mild antibiotic allergy. Front Allergy. 2022;3:1050048. 10.3389/falgy.2022.1050048
2. Pichler WJ. Immune pathomechanism and classification of drug hypersensitivity. Allergy Eur J Allergy Clin Immunol. 2019;74(8):1457–71. (Blackwell) 10.1111/all.13765
3. Pichler WJ Hausmann O. Classification of drug hypersensitivity into allergic, p-i, and pseudo-allergic forms. Int Arch Allergy Immunol. 2017;171(3–4):166–79. 10.1159/000453265
4. Sousa-Pinto B, Fonseca JA, Gomes ER Frequency of self--reported drug allergy: A systematic review and meta-analysis with meta-regression. Ann Allergy Asthma Immunol. 2017;119(4):362–73.e2. 10.1016/j.anai.2017.07.009
5. Warrington R, Silviu-Dan F. Drug allergy. Allergy Asthma Clin Immunol. 2011;7(S1):S10. 10.1186/1710-1492-7-S1-S10
6. Vezir E, Dibek Misirlioglu E, Civelek E, Capanoglu M, Guvenir H, Ginis T, et al. Direct oral provocation tests in non--immediate mild cutaneous reactions related to beta--lactam antibiotics. Pediatr Allergy Immunol. 2016;27(1):50–4. 10.1111/pai.12493
7. Prosty C, Copaescu AM, Gabrielli S, Mule P, Ben-Shoshan M. Pediatric drug allergy. Immunol Allergy Clin North Am. 2022;42(2):433–52. 10.1016/j.iac.2022.01.001
8. Blanca-Lopez N, Atanaskovic-Markovic M, Gomes ER, Kidon M, Kuyucu S, Mori F, et al. An EAACI task force report on allergy to beta-lactams in children: Clinical entities and diagnostic procedures. Pediatr Allergy Immunol. 2021;32(7):1426–36. 10.1111/pai.13529
9. Felix MMR, Kuschnir FC. Direct oral provocation test is safe and effective in diagnosing beta-lactam allergy in low-risk children with mild cutaneous reactions. Front Pharmacol. 2020;11:1223. 10.3389/fphar.2020.01223
10. Moral L, Caubet J-C. Oral challenge without skin tests in children with non-severe beta-lactam hypersensitivity: Time to change the paradigm? Pediatr Allergy Immunol. 2017;28:724–7. 10.1111/pai.12800
11. Romano A, Torres MJ, Castells M, Sanz ML, Blanca M. Diagnosis and management of drug hypersensitivity reactions. J Allergy Clin Immunol. 2011;127(3 Suppl):S67–73. 10.1016/j.jaci.2010.11.047
12. Romano A, Atanaskovic-Markovic M, Barbaud A, Bircher AJ, Brockow K, Caubet JC, et al. Towards a more precise diagnosis of hypersensitivity to beta-lactams—An EAACI position paper. Allergy Eur J Allergy Clin Immunol. 2020;75(6):1300–15. 10.1111/all.14122
13. Aberer W, Bircher A, Romano A, Blanca M, Campi P, Fernandez J, et al. Drug provocation testing in the diagnosis of drug hypersensitivity reactions: General considerations. Allergy Eur J Allergy Clin Immunol. 2003;58(9):854–63. 10.1034/j.1398-9995.2003.00279.x
14. Bousquet P-J, Gaeta F, Bousquet-Rouanet L, Lefrant J-Y, Demoly P, Romano A. Provocation tests in diagnosing drug hypersensitivity. Curr Pharm Design. 2008;14(27):2792-802. 10.2174/138161208786369731
15. Demoly P, Kropf R, Bircher A, Pichler WJ. Drug hypersensitivity: Questionnaire. EAACI interest group on drug hypersensitivity. Allergy. 1999 Sep 54(9):999–1003. 10.1034/j.1398-9995.1999.00247.x
16. Gomes ER, Falcão H. Hipersensibilidade a fármacos: Questionário. Rev Port Imunoalergologia. 2001;8:231–2.
17. Bierman CW, Pierson WE, Zeitz SJ, Hoffman LS, Vanarsdel PP. Reactions associated with ampicillin therapy. JAMA. 1972 May 22;220(8):1098–100. http://jama.jamanetwork.com/
18. Rebelo Gomes E, Fonseca J, Araujo L, Demoly P. Drug allergy claims in children: From self-reporting to confirmed diagnosis. Clin Exp Allergy. 2008;38(1):191–8. 10.1111/j.1365-2222.2007.02870.x
19. Rubio M, Bousquet PJ, Gomes E, Romano A, Demoly P. Results of drug hypersensitivity evaluations in a large group of children and adults. Clin Exp Allergy. 2012;42(1):123–30. 10.1111/j.1365-2222.2011.03887.x
20. Iammatteo M, Alvarez Arango S, Ferastraoaru D, Akbar N, Lee AY, Cohen HW, et al. Safety and outcomes of oral graded challenges to amoxicillin without prior skin testing. J Allergy Clin Immunol Pract. 2019;7(1):236–43. 10.1016/j.jaip.2018.05.008
21. Felix MMR, Kuschnir FC. Direct oral provocation test is safe and effective in diagnosing beta-lactam allergy in low-risk children with mild cutaneous reactions. Front Pharmacol. 2020 Aug 7;11:1223. 10.3389/fphar.2020.01223
22. Zambonino MA, Corzo JL, Muñoz C, Requena G, Ariza A, Mayorga C, et al. Diagnostic evaluation of hypersensitivity reactions to beta-lactam antibiotics in a large population of children. Pediat Allergy Immunol. 2014;25(1):80–7. 10.1111/pai.1215
23. Mirakian R, Leech SC, Krishna MT, Richter AG, Huber PAJ, Farooque S, et al. Management of allergy to penicillins and other beta-lactams. Clin Exp Allergy. 2015;45(2):300–27. 10.1111/cea.12468
24. Böhm R, Proksch E, Schwarz T, Cascorbi I. Drug hypersensitivity—-Diagnosis, genetics and prevention. Dtsch Arztebl Int. 2018;115:501–12. 10.3238/arztebl.2018.0501
25. Mill C, Primeau MN, Medoff E, Lejtenyi C, Keefe AO, Netchiporouk E, et al. Assessing the diagnostic properties of a graded oral provocation challenge for the diagnosis of immediate and non-immediate reactions to amoxicillin in children. JAMA Pediatr. 2016;170(6):e160033. 10.1001/jamapediatrics.2016.0033
26. Exius R, Gabrielli S, Abrams EM, O’Keefe A, Protudjer JLP, Lavine E, et al. Establishing amoxicillin allergy in children through direct graded oral challenge (GOC): Evaluating risk factors for positive challenges, safety, and risk of cross-reactivity to cephalosporines. J Allergy Clin Immunol Pract. 2021;9(11):4060–66. 10.1016/j.jaip.2021.06.057
27. Prieto A, Muñoz C, Bogas G, Fernández-Santamaría R, Palomares F, Mayorga C, et al. Single-dose prolonged drug provocation test, without previous skin testing, is safe for diagnosing children with mild non-immediate reactions to beta-lactams. Allergy Eur J Allergy Clin Immunol. 2021;76(8):2544–54. 10.1111/all.14800
28. Kuniyoshi Y, Tsujimoto Y, Banno M, Taito S, Ariie T, Kubota T, et al. Beta-lactam allergy and drug challenge test in children: A systematic review and meta-analysis. Pediat Res. 2023;93(1):22–30. 10.1038/s41390-022-02076-x
29. Srisuwatchari W, Phinyo P, Chiriac AM, Saokaew S, Kulalert P. The safety of the direct drug provocation test in beta lactam hypersensitivity in children: A systematic review and meta-analysis. J Allergy Clin Immunol Pract. 2023;11(2):506–18. 10.1016/j.jaip.2022.11.035
30. Lee CE, Zembower TR, Fotis MA, Postelnick MJ, Greenberger PA, Peterson LR, et al. The incidence of antimicrobial allergies in hospitalized patients: Implications regarding prescribing patterns and emerging bacterial resistance. Arch Intern Med. 2000 Oct 9;160(18):2819–22. 10.1001/archinte.160.18.2819
31. Koosakulchai V, Sangsupawanich P, Wantanaset D, Jessadapakorn W, Jongvilaikasem P, Yuenyongviwat A. Safety of direct oral provocation testing using the-amoxicillin-2-step-challenge in children with history of non-immediate reactions to amoxicillin. World Allergy Organ J. 2021;14(7):100560. 10.1016/j.waojou.2021.100560
32. Arıkoğlu T, Kuyucu S, Caubet JC. New diagnostıc perspectives in the management of pediatrıc beta-lactam allergy. Pediat Allergy Immunol. 2022;33(3):e13745. 10.1111/pai.13745
33. Pongracic JA, Bock SA, Sicherer SH. Oral food challenge practices among allergists in the United States. J Allergy Clin Immunol. 2012;129(2):564–6. 10.1016/j.jaci.2011.09.024
34. Lezmi G, Alrowaishdi F, Bados-Albiero A, Scheinmann P, de Blic J, Ponvert C. Non-immediate-reading skin tests and prolonged challenges in non-immediate hypersensitivity to beta-lactams in children. Pediat Allergy Immunol. 2018;29(1):84–89. 10.1111/pai.12826
35. Romano A, Blanca M, Torres MJ, Bircher A, Aberer W, Brockow K, et al. Diagnosis of non-immediate reactions to β-lactam antibiotics. Allergy Eur J Allergy Clin Immunol. 2004;59(11):1153–60. 10.1111/j.1398-9995.2004.00678.x
36. Padial A, Antunez C, Blanca-Lopez N, Fernandez, TD, Cornejo-Garcia JA, Mayorga C, et al. Non-immediate reactions to β-lactams: Diagnostic value of skin testing and drug provocation test. Clin Exp Allergy. 2008;38(5):822–8. 10.1111/j.1365-2222.2008.02961.x
37. Kuruvilla M, Shih J, Patel K, Scanlon N. 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(1):57–61. 10.2500/aap.2019.40.4184
38. Atakul G, Köse SS, Atay O, Boyacioglu OK, Al S. Asilsoy S, et al. Oral challenge without penicillin skin tests in children with suspected beta-lactam hypersensitivity. J Child Sci. 2022;12(1):E133–7. 10.1055/s-0042-1757151
39. Chiriac AM, Demoly P. Drug provocation tests: Up-date and novel approaches. Allergy Asthma Clin Immunol. 2013;9(1):12. 10.1186/1710-1492-9-12
40. Torres MJ, Adkinson NF, Caubet JC, Khan DA, Kidon MI, Mendelson L, et al. Controversies in drug allergy: Beta-lactam hypersensitivity testing. J Allergy Clin Immunol Pract. 2019;7(1):40–45. 10.1016/j.jaip.2018.07.051
41. Kitsos N, Cassimos D, Trypsianis G, Xinias I, Roilides E, Grivea I, et al. Drug allergy evaluation in children with suspected mild antibiotic allergy. Front Allergy. 2022;3:1050048. 10.3389/falgy.2022.1050048
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Mar 1, 2023
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Cunha, F., Cunha, I., & Gomes, E. (2023). Safety of direct oral provocation test to delabel reported mild beta-lactam allergy in infants. Allergologia Et Immunopathologia, 52(2), 10-15. https://doi.org/10.15586/aei.v52i2.887
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How to Cite
Cunha, F., Cunha, I., & Gomes, E. (2023). Safety of direct oral provocation test to delabel reported mild beta-lactam allergy in infants. Allergologia Et Immunopathologia, 52(2), 10-15. https://doi.org/10.15586/aei.v52i2.887