Update on Quinolone Allergy
- 553 Downloads
Purpose of Review
Quinolones are a group of synthetic antibiotics widely use as first-line treatment for many infections. There has been an increase in the incidence of hypersensitivity reactions to quinolones in recent years, likely due to increased prescription. The purpose of this review is to summarize the clinical pictures, the methods used for diagnosing and the management of allergic reactions to quinolones.
Allergic reactions to quinolones can be immediate or delayed, being anaphylaxis and maculopapular exanthema respectively the most frequent clinical entities. A precise diagnosis is particularly difficult since clinical history is often unreliable, skin tests can induce false-positive results, and commercial in vitro test are not well validated. Therefore, drug provocation testing is considered the gold standard to establish diagnosis, which is not a risk-free procedure. Cross-reactivity between quinolones is difficult to predict due to the small number of patients included in the few published studies. Moreover, hypersensitivity to quinolones has also been associated with beta-lactam and neuromuscular blocking agent allergies, although further studies are needed to understand the underlying mechanisms. Avoidance of the culprit quinolone is indicated in patients with a diagnosis of hypersensitivity to these drugs. When quinolone treatment is the only therapeutic option available, desensitization is necessary.
This review summarizes the complex diagnostic approach and management of allergic reactions to quinolones.
KeywordsAnaphylaxis Basophil activation test Drug provocation test Maculopapular exanthema Quinolone Skin test
Acute generalized exanthematous pustulosis
Basophil activation test
Drug provocation test
Enzyme-linked immunosorbent assay
Fixed drug eruption
Neuromuscular blocking agent
Skin prick test
Toxic epidermal necrolysis
Acknowledgements and Authors’ Contributions
We thank James R. Perkins for his help with the English language version of this manuscript. MJT and ID compiled the entire manuscript; MJT contributed to the introduction, management, and desensitization and conclusion sections; IA contributed to the classification and chemical structure and in vitro tests sections; EM contributed to the clinical reactions immediate and delayed reactions, clinical history and skin tests sections; ID contributed to the epidemiology and risk factors; drug provocation test and cross-reactivity sections. All authors read and approved the final manuscript.
The present study has been supported by Institute of Health “Carlos III” of the Ministry of Economy and Competitiveness (grants cofunded by European Regional Development Fund (ERDF): RETIC ARADYAL RD16/0006/0001. I Doña holds a Juan Rodes research contract (JR15/00036) from the Carlos III National Health Institute, Spanish Ministry of Economy and Competitiveness (grants cofounded by European Social Fund, ESF).
Compliance with Ethical Standards
Conflict of Interest
None of the authors have any conflict of interest, nor have they received any money for this study. Research is part of their daily activities. All authors had full access to all data and take responsibility for the integrity and accuracy of the data analysis.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 8.• Lobera T, Audicana MT, Alarcon E, Longo N, Navarro B, Munoz D. Allergy to quinolones: low cross-reactivity to levofloxacin. J Investig Allergol Clin Immunol. 2010;20(7):607–11. In this study, authors showed the low cross-reactivity between levofloxacin and ciprofloxacin in patients with immediate hypersensitivity reactions to quinolones, hightlighting the importance of the drug provocation test for finding safe quinolone alternatives. PubMedGoogle Scholar
- 9.González-Gregori R, Dolores Hernández Fernandez De Rojas M, López-Salgueiro R, Díaz-Palacios M, García AN. Allergy alerts in electronic health records for hospitalized patients. Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma & Immunology. 2012;109(2):137–40.Google Scholar
- 10.•• Blanca-Lopez N, Ariza A, Dona I, et al. Hypersensitivity reactions to fluoroquinolones: analysis of the factors involved. Clinical and experimental allergy: journal of the British Society for Allergy and Clinical Immunology. 2013;43(5):560–7. This study showed that fluoroquinolone allergy is more often confirmed in patients with immediate reactions, when moxifloxacin is the quinolone involved and inpatients with hypersensitivity to betalactams. CrossRefGoogle Scholar
- 11.• Sachs B, Riegel S, Seebeck J, et al. Fluoroquinolone-associated anaphylaxis in spontaneous adverse drug reaction reports in Germany: differences in reporting rates between individual fluoroquinolones and occurrence after first-ever use. Drug Saf. 2006;29(11):1087–100. This article concluded that drug-incuced anaphylaxis seems to be associated with the fluoroquinolone administration mainly with moxifloxacin CrossRefPubMedGoogle Scholar
- 12.•• Aranda A, Mayorga C, Ariza A, et al. In vitro evaluation of IgE-mediated hypersensitivity reactions to quinolones. Allergy. 2011;66(2):247–54. In this study, the authors analyzed the value of basophil activation test in the evaluation of IgE mediated reactions to quinolones. They found that the basophil activation test is sensitive and useful for diagnosis. CrossRefPubMedGoogle Scholar
- 18.• Schmid DA, Depta JP, Pichler WJ. T cell-mediated hypersensitivity to quinolones: mechanisms and cross-reactivity. Clinical and experimental allergy: journal of the British Society for Allergy and Clinical Immunology. 2006;36(1):59–69. In this study patterns of recognition of different quinolones by T cell were analyzed in patients with delayed reaction to ciprofloxacin. The results demonstrated that cross-reactivity among the different quinolones is frequent CrossRefGoogle Scholar
- 36.•• Manfredi M, Severino M, Testi S, et al. Detection of specific IgE to quinolones. J Allergy Clin Immunol. 2004;113(1):155–60. This is the first study in demonstrating the presence of specific IgE in patients with quinolone hypersensitivity by radioimmunoassay with sepharose. This study also demonstratedfrequent cross-reactivity within different quinolones. CrossRefPubMedGoogle Scholar
- 52.Gomez E, Blanca-Lopez N, Torres MJ, et al. Immunoglobulin E-mediated immediate allergic reactions to dipyrone: value of basophil activation test in the identification of patients. Clinical and experimental allergy: journal of the British Society for Allergy and Clinical Immunology. 2009;39(8):1217–24.CrossRefGoogle Scholar
- 57.Demir S GA, Akdeniz N, Aktas-Cetin E, et al.. Usefulness of in vivo and in vitro diagnostic tests in the diagnosis of hypersensitivity reactions to quinolones and in the evaluation of cross-reactivity: a comprehensive study including the latest quinolone gemifloxacin. Allergy Asthma Immunol Res. 2017;9(4):347–59.Google Scholar
- 70.•• Rouzaire P, Nosbaum A, Mullet C, et al. Immediate allergic hypersensitivity to quinolones associates with neuromuscular blocking agent sensitization. J Allergy Clin Immunol Pract. 2013;1(3):273–9 e1. In this study authors found a high prevalence of quaternary ammonium sensitization in patients with immediate hypersensitivity to quinolone, however the clinical relevance of this finding should be further analyzed. This could explain that in some cases quinolone hypersensitivity happens after the first drug exposition. CrossRefPubMedGoogle Scholar