Allergy to beta-lactam antibiotics in children: Risk factors for a positive diagnostic work-up

Main Article Content

E. Dias de Castro
F. Carolino
L. Carneiro-Leão
J. Barbosa
L. Ribeiro
J.R. Cernadas

Keywords

Drug allergy, Beta-lactam antibiotics, Children, Allergy diagnostic work-up, Risk factors

Abstract

Background: Allergy to beta-lactam (L) antibiotics is highly reported in children, but rarely confirmed. Risk factors for a positive diagnostic work-up are scarce.


The primary aim was to characterize the cases of children with confirmed L allergy, investigating potential risk factors. Secondary aims were to assess the prevalence of allergy to L in this population and to confirm the safety of less extensive diagnostic protocols for milder reactions.


Methods: We reviewed the clinical data from all children evaluated in our Department for suspected L allergy, over a six-year period.


Results: Two hundred and twenty children (53% females) with a mean age of 6.5 ± 4.2 years were evaluated. Cutaneous manifestations were the most frequently reported (96.9%), mainly maculopapular exanthema (MPE). The reactions were non-immediate in 59.5% of the cases.


Only 23 children (10.5%) were diagnosed with allergy to L. The likelihood of L allergy was significantly higher in children with a  family history of drug allergy (p < 0.001) and in those with a smaller time period between the reaction and the study (p = 0.046). The probability of not confirming L allergy is greater in children reporting less severe reactions (p < 0.001) and MPE (p < 0.001).


We found the less extensive diagnostic protocol in milder reactions safe, since only 4.2% of the children presented a positive provocation test (similar reaction as the index reaction).


Conclusion: This study highlights family history of drug allergy as a risk factor for a positive diagnostic work-up. Larger series are required, particularly genetic studies to accurately determine future risk for L allergy in children.

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References

1. Azevedo J, Gaspar Â, Mota I, Benito-Garcia F, Alves-Correia M, Chambel M, et al. Anaphylaxis to beta-lactam antibiotics at pediatric age: six-year survey. Allergol Immunopathol (Madr). 2019;47:128-32.

2. Abrams EM, Atkinson AR, Wong T, Ben-Shoshan M. The importance of delabeling -lactam allergy in children. J Pediatr. 2019;204, 291-7.e1.

3. Gomes ER, Brockow K, Kuyucu S, Sarreta F, Mori F, Blanca Lopez N, et al. Drug hypersensitivity in children: report from the pediatric task force of the EAACI Drug Allergy Interest Group. Allergy. 2016;71:149-61.

4. Graham F, Tsabouri S, Caubet JC. Hypersensitivity reactions to beta-lactams in children. Curr Opin Allergy Clin Immunol. 2018;18:284-90.

5. Regateiro FS, Rezende I, Pinto I, Abreu C, Carreiro-Martins P, Gomes ER. Short and extended provocation tests have similar negative predictive value in non-immediate hypersensitivity to beta-lactams in children. Allergol Immunopathol (Madr). 2019;7:40-5.

6. Lucas M, Arnold A, Sommerfield A, Trevenen M, Braconnier L, Schilling A, et al. Antibiotic allergy labels in children are associated with adverse clinical outcomes. J Allergy Clin Immunol Pract. 2019;7:975-82.

7. Ponvert C, Perrin Y, Bados-Albiero A, Le Bourgeois M, Karila C, Delaccourt C, et al. Allergy to betalactam antibiotics in children: results of a 20-year study based on clinical history, skin and challenge tests. Pediatr Allergy Immunol. 2011;22:411-8.

8. Zambonino MA, Corzo JL, Munoz C, Requena G, Ariza A, Mayorga C, et al. Diagnostic evaluation of hyper-sensitivity reactions to beta-lactam antibiotics in a large population of children. Pediatr Allergy Immunol. 2014;25:80-7.

9. Abrams EM, Wakeman A, Gerstner TV, Warrington RJ, Singer AG. Prevalence of beta-lactam allergy: a retrospective chart review of drug allergy assessment in a predominantly pediatric population. Allergy Asthma Clin Immunol. 2016;12:59.

10. Mill C, Primeau MN, Medoff E, Lejtenyi C, O’Keefe A, 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:e160033.

11. Simsek IE, Cogurlu MT, Aydogan M. Suspected reaction with cephalosporin may be a predictive factor for -lactam allergy in children. Int Arch Allergy Immunol. 2019;178:248-54.

12. Diaferio L, Chiriac AM, Leoni MC, Castagnoli R, Caimmi S, Miniello VL, et al. Skin tests are important in children with-lactam hypersensitivity, but may be reduced in number. Pediatr Allergy Immunol. 2019;30:462---8.

13. Sousa-Pinto B, Araújo L, Freitas A, Delgado L. Hospitalizations in children with a penicillin allergy label: an assessment of healthcare impact. Int Arch Allergy Immunol. 2018;176:234-8.

14. Demoly P, Adkinson N, Brockow K, Castells M, Chiriac AM, Greenberger PA, et al. International Consensus on drug allergy. Allergy. 2014;69:420-37.

15. Demoly P, Kropf R, Bircher A, Pichler WJ. Drug hypersensitivity questionnaire (ENDA-EAACI). Allergy. 1999;54:999-1003.

16. Brockow K, Romano A, Blanca M, Ring J, Pichler W, Demoly P. General considerations for skin test procedures in the diagnosis of drug hypersensitivity. Allergy. 2002;57:45-51.

17. Brokow K, Garvey LH, Aberer W, Atanaskovic-Markovic M, Barbaud A, Bilo MB, et al. Skin test concentrations for systemically administered drugs-ENDA-EAACI Drug Allergy Interest Group position paper. Allergy. 2013;68:702-12.

18. Aberer W, Bircher A, Romano A, Blanca M, Campi P, Fernadez J, et al. Drug provocation testing in the diagnosis of drug hypersensitivity reactions. Allergy. 2003;58:854-63.

19. Blanca M, Romano A, Torres MJ, Fernandez J, Mayorga C, Rodrigues J, et al. Update on the evaluation of hypersensitivity reactions to betalactams. Allergy. 2009;64:183-93.

20. Caubet JC, Kaiser L, Lemaitre B, Fellay B, Gervaix A, Eigenmann PA. The role of penicillin benign skin rashes in childhood: a prospective study based on drug rechallenge. J Allergy Clin Immunol. 2011;127:218-22.

21. Blanca-Lopez N, Zapatero L, Alonso E, Torres MJ, Fuentes V, Martinez-Molero MI, et al. Skin testing and drug provocation in the diagnosis of nonimmediate reactions to aminopenicillins in children. Allergy. 2009;64:229-33.

22. Oussalah A, Mayorga C, Blanca M, Barbaud A, Nakonechna A, Cernadas J, et al. Genetic variants associated with drugs-induced immediate hypersensitivity reactions: a PRISMAcompliant systematic review. Allergy. 2016;71:443-62.

23. Gueant JL, Romano A, Cornejo-Garcia JA, Oussalah A, Chery C, Blanca-Lopez N, et al. HLA-DRA variants predict penicillin allergy in genome-wide fine-mapping genotyping. J Allergy Clin Immunol. 2015;135:253-9.

24. Moral L, Caubet JC. 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.

25. Vyles D, Adams J, Chiu A, Simpson P, Niller M, Brousseau DC. Allergy testing in children with low-risk penicillin allergy symptoms. Pediatrics. 2017;140:e20170471.

26. Atanaskovic-Markovic M, Gaeta F, Medjo B, Gavrovic-Jankulovic M, Velickovic TC, Tmusic V, et al. Non-immediate hypersensitivity reactions to beta-lactam antibiotics in children - our 10-year experience in allergy work-up. Pediatr Allergy Immunol. 2016;27:533-8.