SpringerLink
Log in

Diagnostic evaluation of hypersensitivity reactions to arylpropionic acid derivatives: a descriptive observational study focusing on clinical characteristics and potential risk factors in children

  • Research Article
  • Published:
International Journal of Clinical Pharmacy Aims and scope Submit manuscript

Abstract

Background

Arylpropionic acid derivatives (APs) are the main triggers of nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity. Data on clinical patterns and risk factors for AP hypersensitivity in children are quite limited.

Aim

To assess the clinical characteristics and potential risk factors for proven AP hypersensitivity in children.

Method

Patients with a history of AP hypersensitivity were retrospectively assessed using a standardized diagnostic algorithm. Children with confirmed hypersensitivity were defined as selective responders or cross-intolerants based on the result of drug provocation tests and further categorized according to the EAACI/ENDA classification. A multivariable logistic regression analysis was performed to analyze the potential risk factors for proven AP hypersensitivity.

Results

A total of 166 patients (51.2% male, median age of six years) with a history of AP hypersensitivity were included. Ibuprofen (89.2%) was the most frequently reported AP in the patients’ histories. The reported hypersensitivity of 40 (22.4%) patients was confirmed by diagnostic testing: eight (13.6%) patients with a history of reaction only to APs and 32 (29.9%) patients with a history of reactions to multiple NSAIDs, including chemically unrelated NSAIDs in addition to APs. Five (12.5%) patients were classified as selective responders and 35 (87.5%) were cross-intolerants. Overall, five (12.5%) of the confirmed cases could not be categorized according to the EAACI/ENDA classification. Older age (aOR: 1.11, 95% CI 1.02–1.21, p = 0.015), chronic urticaria as an underlying disease (aOR: 2.87, 95% CI 1.09–7.54, p = 0.033) and a history of anaphylaxis (aOR: 7.84, 95% CI 1.86–33.04, p = 0.005) were related to confirmed AP hypersensitivity.

Conclusion

Almost a quarter of children and adolescents were confirmed to have AP hypersensitivity. Older age, the presence of chronic urticaria and a history of anaphylaxis were potential risk factors for proven AP hypersensitivity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Germany)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Mori F, Atanaskovic-Markovic M, Blanca-Lopez N, et al. A Multicenter retrospective study on hypersensitivity reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) in children: a report from the European Network on Drug Allergy (ENDA) group. J Allergy Clin Immunol Pract. 2020;8:1022-1031.e1021.

    Article  PubMed  Google Scholar 

  2. Doña I, Blanca-López N, Cornejo-García JA, et al. Drug hypersensitivity reactions: response patterns, drug involved and temporal variations in a large series of patients. J Investig Allergol Clin Immunol. 2012;22(5):363–71.

    PubMed  Google Scholar 

  3. Kowalski ML, Asero R, Bavbek S, et al. Classification and practical approach to the diagnosis and management of hypersensitivity to nonsteroidal anti-inflammatory drugs. Allergy. 2013;68:1219–32.

    Article  CAS  PubMed  Google Scholar 

  4. Cousin M, Chiriac A, Molinari N, et al. Phenotypical characterization of children with hypersensitivity reactions to NSAIDs. Pediatr Allergy Immunol. 2016;27:743–8.

    Article  PubMed  Google Scholar 

  5. Cavkaytar O, Arik Yilmaz E, Karaatmaca B, et al. Different phenotypes of non-steroidal anti-inflammatory drug hypersensitivity during childhood. Int Arch Allergy Immunol. 2015;167:211–21.

    Article  CAS  PubMed  Google Scholar 

  6. Guvenir H, Dibek Misirlioglu E, Vezir E, et al. Nonsteroidal anti-inflammatory drug hypersensitivity among children. Allergy Asthma Proc. 2015;36:386–93.

    Article  CAS  PubMed  Google Scholar 

  7. Arikoglu T, Aslan G, Yildirim DD, et al. Discrepancies in the diagnosis and classification of nonsteroidal anti-inflammatory drug hypersensitivity reactions in children. Allergol Int. 2017;66:418–24.

    Article  CAS  PubMed  Google Scholar 

  8. Zambonino MA, Torres MJ, Muñoz C, et al. Drug provocation tests in the diagnosis of hypersensitivity reactions to non-steroidal anti-inflammatory drugs in children. Pediatr Allergy Immunol. 2013;24:151–9.

    Article  PubMed  Google Scholar 

  9. Jares EJ, Villa RC, Sánchez-Borges M, et al. Drug-Induced anaphylaxis, elicitors, risk factors and management in Latin America. J Allergy Clin Immunol Pract. 2020;8(4):1403-1405.e1.

    Article  PubMed  Google Scholar 

  10. Bindu S, Mazumder S, Bandyopadhyay U. Non-steroidal anti-inflammatory drugs (NSAIDs) and organ damage: a current perspective. Biochem Pharmacol. 2020;180: 114147.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Cavkaytar O, Arga M. NSAID hypersensitivity in the pediatric population: classification and diagnostic strategies. J Asthma Allergy. 2022;15:1383–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Kidon M, Blanca-Lopez N, Gomes E, et al. EAACI/ENDA position paper: diagnosis and management of hypersensitivity reactions to non-steroidal anti-inflammatory drugs (NSAIDs) in children and adolescents. Pediatr Allergy Immunol. 2018;29:469–80.

    Article  PubMed  Google Scholar 

  13. Blanca-Lopez N, Soriano V, Garcia-Martin E, et al. NSAID-induced reactions: classification, prevalence, impact, and management strategies. J Asthma Allergy. 2019;12:217–33.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Walters KM, Woessner KM. An overview of nonsteroidal antiinflammatory drug reactions. Immunol Allergy Clin North Am. 2016;36:625–41.

    Article  PubMed  Google Scholar 

  15. Lee Y, Shin YS, Park HS. New phenotypes in hypersensitivity reactions to nonsteroidal anti-inflammatory drugs. Curr Opin Allergy Clin Immunol. 2019;19:302–7.

    Article  CAS  PubMed  Google Scholar 

  16. Blanca-Lopez N, Somoza-Alvarez ML, Bellon T, et al. NSAIDs hypersensitivity: questions not resolved. Curr Opin Allergy Clin Immunol. 2018;18:291–301.

    Article  CAS  PubMed  Google Scholar 

  17. Demoly P, Kropf R, Bircher A, et al. Drug hypersensitivity: questionnaire. EAACI interest group on drug hypersensitivity. Allergy. 1999;54:999–1003.

    Article  CAS  PubMed  Google Scholar 

  18. Brockow K, Romano A, Blanca M, et al. General considerations for skin test procedures in the diagnosis of drug hypersensitivity. Allergy. 2002;57:45–51.

    Article  CAS  PubMed  Google Scholar 

  19. Brockow K, Garvey LH, Aberer W, et al. Skin test concentrations for systemically administered drugs—an ENDA/EAACI drug allergy interest group position paper. Allergy. 2013;68:702–12.

    Article  CAS  PubMed  Google Scholar 

  20. Yilmaz O, Ertoy Karagol IH, Bakirtas A, et al. Challenge-proven nonsteroidal anti-inflammatory drug hypersensitivity in children. Allergy. 2013;68:1555–61.

    Article  CAS  PubMed  Google Scholar 

  21. Ertoy Karagol HI, Yilmaz O, Topal E, et al. Nonsteroidal anti-inflammatory drugs-exacerbated respiratory disease in adolescents. Int Forum Allergy Rhinol. 2015;5:392–8.

    Article  PubMed  Google Scholar 

  22. Nizankowska-Mogilnicka E, Bochenek G, Mastalerz L, et al. EAACI/GA2LEN guideline: aspirin provocation tests for diagnosis of aspirin hypersensitivity. Allergy. 2007;62:1111–8.

    Article  CAS  PubMed  Google Scholar 

  23. Aberer W, Bircher A, Romano A, et al. Drug provocation testing in the diagnosis of drug hypersensitivity reactions: general considerations. Allergy. 2003;58:854–63.

    Article  CAS  PubMed  Google Scholar 

  24. Bousquet PJ, Gaeta F, Bousquet-Rouanet L, et al. Provocation tests in diagnosing drug hypersensitivity. Curr Pharm Des. 2008;14:2792–802.

    Article  CAS  PubMed  Google Scholar 

  25. Corzo JL, Zambonino MA, Muñoz C, et al. Tolerance to COX-2 inhibitors in children with hypersensitivity to nonsteroidal anti-inflammatory drugs. Br J Dermatol. 2014;170:725–9.

    Article  CAS  PubMed  Google Scholar 

  26. Kidon MI, Liew WK, Chiang WC, et al. Hypersensitivity to paracetamol in Asian children with early onset of nonsteroidal anti-inflammatory drug allergy. Int Arch Allergy Immunol. 2007;144:51–6.

    Article  CAS  PubMed  Google Scholar 

  27. Alves C, Romeira AM, Abreu C, et al. Non-steroidal anti-inflammatory drug hypersensitivity in children. Allergol Immunopathol (Madr). 2017;45:40–7.

    Article  CAS  PubMed  Google Scholar 

  28. Eser Simsek I, Cogurlu MT, Aydogan M. Two approaches for diagnosis of nonsteroidal anti-inflammatory drug hypersensitivity in children. Ann Allergy Asthma Immunol. 2019;123:389–93.

    Article  CAS  PubMed  Google Scholar 

  29. Topal E, Celiksoy MH, Catal F, et al. The value of the clinical history for the diagnosis of immediate nonsteroidal anti-inflammatory drug hypersensitivity and safe alternative drugs in children. Allergy Asthma Proc. 2016;37:57–63.

    Article  CAS  PubMed  Google Scholar 

  30. Minaldi E, Cahill K. Recent updates in understanding NSAID hypersensitivity. Curr Allergy Asthma Rep. 2023;23:181–8.

    Article  CAS  PubMed  Google Scholar 

  31. Doña I, Pérez-Sánchez N, Eguiluz-Gracia I, et al. Progress in understanding hypersensitivity reactions to nonsteroidal anti-inflammatory drugs. Allergy. 2020;75:561–75.

    Article  PubMed  Google Scholar 

  32. Gaffar J, Gabrielli S, Lavine E, et al. Diagnosis of Ibuprofen allergy through oral challenge. Clin Exp Allergy. 2020;50:636–9.

    Article  PubMed  Google Scholar 

  33. Salas-Casinello M, Sáenz-de Santa María R, López-Sánchez JD, et al. Different patterns of response in hypersensitivity reactions to arylpropionic acid derivatives. J Allergy Clin Immunol Pract. 2023;11(12):3715–23.

    Article  CAS  PubMed  Google Scholar 

  34. Blanca-López N, Pérez-Alzate D, Andreu I, et al. Immediate hypersensitivity reactions to ibuprofen and other arylpropionic acid derivatives. Allergy. 2016;71(7):1048–56.

    Article  PubMed  Google Scholar 

  35. Blanca-López N, Haroun-Diaz E, Ruano FJ, et al. Acetyl salicylic acid challenge in children with hypersensitivity reactions to nonsteroidal anti-inflammatory drugs differentiates between cross-intolerant and selective responders. J Allergy Clin Immunol Pract. 2018;6(4):1226–35.

    Article  PubMed  Google Scholar 

  36. Pérez-Sánchez N, Doña I, Bogas G, et al. Evaluation of subjects experiencing allergic reactions to non-steroidal anti-inflammatory drugs: clinical characteristics and drugs involved. Front Pharmacol. 2020;11:503.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Arikoglu T, Tokmeci N, Demirhan A, et al. Evaluation of different protocols for classification of pediatric hypersensitivity reactions to nonsteroidal anti-inflammatory drugs: children with underlying allergic disease should be a separate subgroup. Allergy Asthma Proc. 2024;45(1):14–23.

    Article  CAS  PubMed  Google Scholar 

  38. Hur GY, Park HS. Clinical characteristics of NSAID-induced blended reaction. Allergy Asthma Immunol Res. 2021;13:171–2.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Yilmaz Topal O, Kulhas Celik I, Turgay Yagmur I, et al. Results of NSAID provocation tests and difficulties in the classification of children with nonsteroidal anti-inflammatory drug hypersensitivity. Ann Allergy Asthma Immunol. 2020;125(2):202–7.

    Article  CAS  PubMed  Google Scholar 

  40. Doña I, Barrionuevo E, Salas M, et al. NSAIDs-hypersensitivity often induces a blended reaction pattern involving multiple organs. Sci Rep. 2018;8:16710.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Cavkaytar O, du Toit G, Caimmi D. Characteristics of NSAID-induced hypersensitivity reactions in childhood. Pediatr Allergy Immunol. 2019;30:25–35.

    Article  PubMed  Google Scholar 

  42. Sánchez-Borges M, Capriles-Hulett A. Atopy is a risk factor for non-steroidal anti-inflammatory drug sensitivity. Ann Allergy Asthma Immunol. 2000;84:101–6.

    Article  PubMed  Google Scholar 

  43. Sánchez-Borges M, Capriles-Behrens E, Caballero-Fonseca F. Hypersensitivity to non-steroidal anti-inflammatory drugs in childhood. Pediatr Allergy Immunol. 2004;15(4):376–80.

    Article  PubMed  Google Scholar 

  44. Hassani A, Ponvert C, Karila C, et al. Hypersensitivity to cyclooxygenase inhibitory drugs in children: a study of 164 cases. Eur J Dermatol. 2008;18(5):561–5.

    CAS  PubMed  Google Scholar 

  45. Podlecka D, Socha-Banasiak A, Jerzynska J, et al. Practical approach to hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) in children. Pharmaceuticals (Basel). 2023;16(9):1237.

    Article  CAS  PubMed  Google Scholar 

  46. Imbalzano E, Casciaro M, Quartuccio S, et al. Association between urticaria and virus infections: a systematic review. Allergy Asthma Proc. 2016;37(1):18–22.

    Article  PubMed  Google Scholar 

  47. Kidon MI, Kang LW, Chin CW, et al. Early presentation with angioedema and urticaria in cross-reactive hypersensitivity to nonsteroidal antiinflammatory drugs among young, Asian, atopic children. Pediatrics. 2005;116:e675-680.

    Article  PubMed  Google Scholar 

  48. Cavkaytar O, Arik Yilmaz E, Buyuktiryaki B, et al. Challenge-proven aspirin hypersensitivity in children with chronic spontaneous urticaria. Allergy. 2015;70(2):153–60.

    Article  CAS  PubMed  Google Scholar 

  49. Pascal M, Muñoz-Cano R, Milà J, et al. Nonsteroidal anti-inflammatory drugs enhance IgE-mediated activation of human basophils in patients with food anaphylaxis dependent on and independent of nonsteroidal anti-inflammatory drugs. Clin Exp Allergy. 2016;46:1111–9.

    Article  CAS  PubMed  Google Scholar 

  50. Matsuo H, Yokooji T, Morita H, et al. Aspirin augments IgE-mediated histamine release from human peripheral basophils via Syk kinase activation. Allergol Int. 2013;62:503–11.

    Article  CAS  PubMed  Google Scholar 

  51. Suzuki Y, Ra C. Analysis of the mechanism for the development of allergic skin inflammation and the application for its treatment: aspirin modulation of IgE-dependent mast cell activation: role of aspirin-induced exacerbation of immediate allergy. J Pharmacol Sci. 2009;110:237–44.

    Article  CAS  PubMed  Google Scholar 

  52. Ensina LF, de Lacerda AE, de Andrade DM, et al. Drug-induced anaphylaxis in children: nonsteroidal anti-inflammatory drugs and drug provocation test. J Allergy Clin Immunol Pract. 2014;2:825.

    Article  PubMed  Google Scholar 

  53. Ganapathy S, Lwin Z, Ting DH, et al. Anaphylaxis in children: experience of 485 episodes in 1,272,482 patient attendances at a tertiary paediatric emergency department from 2007 to 2014. Ann Acad Med Singap. 2016;45:542–8.

    Article  PubMed  Google Scholar 

  54. Blanca-López N, Cornejo-García JA, Plaza-Serón MC, et al. Hypersensitivity to nonsteroidal anti-inflammatory drugs in children and adolescents: cross-intolerance reactions. J Investig Allergol Clin Immunol. 2015;25:259–69.

    PubMed  Google Scholar 

  55. Kowalski ML, Makowska JS. Seven steps to the diagnosis of NSAIDs hypersensitivity: how to apply a new classification in real practice? Allergy Asthma Immunol Res. 2015;7(4):312–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

No funding.

Author information

Authors and Affiliations

  1. Department of Pediatric Allergy and Immunology, Faculty of Medicine, Mersin University, Çiftlikköy Kampüsü, Yenişehir, Mersin, Turkey

    Tugba Arikoglu, Aylin Kont Ozhan, Aysu İlhan Yalaki, Veysi Akbey & Semanur Kuyucu

  2. Department of Pediatric Allergy and Immunology, Adıyaman University Training and Research Hospital, Adıyaman, Turkey

    Nazan Tokmeci

  3. Department of Pediatric Allergy and Immunology, Mersin City Training and Research Hospital, Mersin, Turkey

    Ali Demirhan

Authors
  1. Tugba Arikoglu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nazan Tokmeci
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ali Demirhan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Aylin Kont Ozhan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Aysu İlhan Yalaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Veysi Akbey
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Semanur Kuyucu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tugba Arikoglu.

Ethics declarations

Conflicts of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 24 kb)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Arikoglu, T., Tokmeci, N., Demirhan, A. et al. Diagnostic evaluation of hypersensitivity reactions to arylpropionic acid derivatives: a descriptive observational study focusing on clinical characteristics and potential risk factors in children. Int J Clin Pharm (2024). https://doi.org/10.1007/s11096-024-01756-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11096-024-01756-4

Keywords

Search

Navigation