Clinical Characterization and Diagnostic Approaches for Patients Reporting Hypersensitivity Reactions to Quinolones

[EN] BACKGROUND: Quinolones are the second most frequent cause of hypersensitivity reactions (HSRs) to antibiotics. A marked increase in the number of patients with HSRs to quinolones has been detected. OBJECTIVE: To describe the clinical characteristics of patients with HSRs to quinolones and present methods for their diagnosis. METHODS: Patients attending the allergy unit due to reactions suggestive of HSRs to quinolones were prospectively evaluated between 2005 and 2018. Diagnosis was achieved using clinical history, skin tests (STs), basophil activation tests (BATs), and drug provocation tests (DPTs) if ST and BAT results were negative. RESULTS: We included 128 subjects confirmed as having HSRs to quinolones and 42 found to be tolerant. Anaphylaxis was the most frequent entity in immediate HSRs and was most commonly induced by moxifloxacin. Patients were evaluated a median of 150 days (interquartile range, 60-365 days) after the reaction. Of patients who underwent ST and BAT, 40.7% and 70%, respectively, were positive. DPT with a quinolone was performed in 48 cases, giving results depending on the culprit drug: when moxifloxacin was involved, 62.5% of patients gave a positive DPT result to ciprofloxacin, whereas none reacted to levofloxacin. The risk of HSR was 96 times higher in subjects who reported moxifloxacin-induced anaphylaxis and 18 times higher in those reporting immediate reactions compared with clinical entities induced by quinolones other than moxi-floxacin and nonimmediate reactions. CONCLUSIONS: The diagnosis of HSR to quinolones is complex. The use of clinical history is essential as a first step. BAT shows higher sensitivity than STs. DPTs can be useful for finding safe alternative quinolones.The present study has been supported by the Institute of Health "Carlos III" of the Ministry of Economy and Competitiveness (grants cofounded by European Regional Development Fund: RETIC ARADYALRD16/0006/0001, RD16/0006/0010, RD16/0006/0019, and RD16/0006/0030). I.D. is a clinical investigator (B0001-2017) from Consejeria de Salud of the Andalusian government, Junta de Andalucia. N.P.-S. holds a Rio Hortega research contract (CM17/0014), and E.B. a Juan Rodes research contract (JR18/00049), both from the Institute of Health "Carlos III," Spanish Ministry of Economy and Competitiveness (grants cofounded by the European Social Fund).Doña, I.; Pérez-Sánchez, N.; Salas, M.; Barrionuevo, E.; Ruiz-San Francisco, A.; Hernández Fernández De Rojas, D.; Martí-Garrido, J.... (2020). Clinical Characterization and Diagnostic Approaches for Patients Reporting Hypersensitivity Reactions to Quinolones. Journal of Allergy and Clinical Immunology: In Practice. 8(8):2707-2714. https://doi.org/10.1016/j.jaip.2020.04.0512707271488Campi, P., & Pichler, W. J. (2003). Quinolone hypersensitivity. Current Opinion in Allergy and Clinical Immunology, 3(4), 275-281. doi:10.1097/00130832-200308000-00007Zhanel, G. G., Ennis, K., Vercaigne, L., Walkty, A., Gin, A. S., Embil, J., … Hoban, D. J. (2002). A Critical Review of the Fluoroquinolones. Drugs, 62(1), 13-59. doi:10.2165/00003495-200262010-00002Bertino, J., & Fish, D. (2000). The safety profile of the fluoroquinolones. Clinical Therapeutics, 22(7), 798-817. doi:10.1016/s0149-2918(00)80053-3Ho, D. Y., Song, J. C., & Wang, C. C. (2003). Anaphylactoid Reaction to Ciprofloxacin. Annals of Pharmacotherapy, 37(7-8), 1018-1023. doi:10.1345/aph.1c498Demoly, P., Adkinson, N. F., Brockow, K., Castells, M., Chiriac, A. M., Greenberger, P. A., … Thong, B. Y.-H. (2014). International Consensus on drug allergy. Allergy, 69(4), 420-437. doi:10.1111/all.12350Schmid, D. A., Depta, J. P. H., & Pichler, W. J. (2006). T cell-mediated hypersensitivity to quinolones: mechanisms and cross-reactivity. Clinical Experimental Allergy, 36(1), 59-69. doi:10.1111/j.1365-2222.2006.02402.xJones, S. C., Budnitz, D. S., Sorbello, A., & Mehta, H. (2013). US-based emergency department visits for fluoroquinolone-associated hypersensitivity reactions. Pharmacoepidemiology and Drug Safety, 22(10), 1099-1106. doi:10.1002/pds.3499Sachs, B., Fischer-Barth, W., & Merk, H. F. (2015). Reporting rates for severe hypersensitivity reactions associated with prescription-only drugs in outpatient treatment in Germany. Pharmacoepidemiology and Drug Safety, 24(10), 1076-1084. doi:10.1002/pds.3857McNeil, B. D., Pundir, P., Meeker, S., Han, L., Undem, B. J., Kulka, M., & Dong, X. (2014). Identification of a mast-cell-specific receptor crucial for pseudo-allergic drug reactions. Nature, 519(7542), 237-241. doi:10.1038/nature14022Van Gasse, A. L., Sabato, V., Uyttebroek, A. P., Elst, J., Faber, M. A., Hagendorens, M. M., … Ebo, D. G. (2017). Immediate moxifloxacin hypersensitivity: Is there more than currently meets the eye? Allergy, 72(12), 2039-2043. doi:10.1111/all.13236Porebski, G., Kwiecien, K., Pawica, M., & Kwitniewski, M. (2018). Mas-Related G Protein-Coupled Receptor-X2 (MRGPRX2) in Drug Hypersensitivity Reactions. Frontiers in Immunology, 9. doi:10.3389/fimmu.2018.03027González-Gregori, R., Dolores Hernández Fernandez De Rojas, M., López-Salgueiro, R., Díaz-Palacios, M., & García, A. N. (2012). Allergy alerts in electronic health records for hospitalized patients. Annals of Allergy, Asthma & Immunology, 109(2), 137-140. doi:10.1016/j.anai.2012.06.006Renaudin, J.-M., Beaudouin, E., Ponvert, C., Demoly, P., & Moneret-Vautrin, D.-A. (2013). Severe drug-induced anaphylaxis: analysis of 333 cases recorded by the Allergy Vigilance Network from 2002 to 2010. Allergy, 68(7), 929-937. doi:10.1111/all.12168Blanca-López, N., Ariza, A., Doña, I., Mayorga, C., Montañez, M. I., Garcia-Campos, J., … Torres, M. J. (2013). Hypersensitivity reactions to fluoroquinolones: analysis of the factors involved. Clinical & Experimental Allergy, 43(5), 560-567. doi:10.1111/cea.12099Johannes, C. B., Ziyadeh, N., Seeger, J. D., Tucker, E., Reiter, C., & Faich, G. (2007). Incidence of Allergic Reactions Associated with Antibacterial Use in a Large, Managed Care Organisation. Drug Safety, 30(8), 705-713. doi:10.2165/00002018-200730080-00007Kulthanan, K., Chularojanamontri, L., Manapajon, A., Dhana, N., & Jongjarearnprasert, K. (2011). Cutaneous Adverse Reactions to Fluoroquinolones. Dermatitis, 22(3), 155-160. doi:10.2310/6620.2011.10115Neuman, M. G., Cohen, L. B., & Nanau, R. M. (2015). Quinolones-induced hypersensitivity reactions. Clinical Biochemistry, 48(10-11), 716-739. doi:10.1016/j.clinbiochem.2015.04.006Phillips, C. J., Gilchrist, M., Cooke, F. J., Franklin, B. D., Enoch, D. A., Murphy, M. E., … Holmes, A. H. (2019). Adherence to antibiotic guidelines and reported penicillin allergy: pooled cohort data on prescribing and allergy documentation from two English National Health Service (NHS) trusts. BMJ Open, 9(2), e026624. doi:10.1136/bmjopen-2018-026624Dávila, I., Diez, M. L., Quirce, S., Fraj, J., Hoz, B., & Lazaro, M. (1993). Cross-reactivity between quinolones. Allergy, 48(5), 388-390. doi:10.1111/j.1398-9995.1993.tb02413.xScherer, K., & Bircher, A. J. (2005). Hypersensitivity reactions to fluoroquinolones. Current Allergy and Asthma Reports, 5(1), 15-21. doi:10.1007/s11882-005-0049-1Brockow, K., Garvey, L. H., Aberer, W., Atanaskovic-Markovic, M., Barbaud, A., … Bilo, M. B. (2013). Skin test concentrations for systemically administered drugs - an ENDA/EAACI Drug Allergy Interest Group position paper. Allergy, 68(6), 702-712. doi:10.1111/all.12142Manfredi, M., Severino, M., Testi, S., Macchia, D., Ermini, G., Pichler, W. J., & Campi, P. (2004). Detection of specific IgE to quinolones. Journal of Allergy and Clinical Immunology, 113(1), 155-160. doi:10.1016/j.jaci.2003.09.035Aranda, A., Mayorga, C., Ariza, A., Doña, I., Rosado, A., Blanca-Lopez, N., … Torres, M. J. (2010). In vitro evaluation of IgE-mediated hypersensitivity reactions to quinolones. Allergy, 66(2), 247-254. doi:10.1111/j.1398-9995.2010.02460.xBen Said, B., Berard, F., Bienvenu, J., Nicolas, J.-F., & Rozieres, A. (2010). Usefulness of basophil activation tests for the diagnosis of IgE-mediated allergy to quinolones. Allergy, 65(4), 535-536. doi:10.1111/j.1398-9995.2009.02213.xMayorga, C., Celik, G., Rouzaire, P., Whitaker, P., Bonadonna, P., … Rodrigues-Cernadas, J. (2016). In vitrotests for drug hypersensitivity reactions: an ENDA/EAACI Drug Allergy Interest Group position paper. Allergy, 71(8), 1103-1134. doi:10.1111/all.12886Seitz, C. S., Bröcker, E. B., & Trautmann, A. (2009). Diagnostic testing in suspected fluoroquinolone hypersensitivity. Clinical & Experimental Allergy, 39(11), 1738-1745. doi:10.1111/j.1365-2222.2009.03338.xBrockow, K., Ardern‐Jones, M. R., Mockenhaupt, M., Aberer, W., Barbaud, A., Caubet, J., … Mortz, C. G. (2018). EAACI position paper on how to classify cutaneous manifestations of drug hypersensitivity. Allergy, 74(1), 14-27. doi:10.1111/all.13562Valdivieso, R., Pola, J., Losada, E., Subiza, J., Armentia, A., & Zapata, C. (1988). Severe anaphylactoid reaction to nalidixic acid. Allergy, 43(1), 71-73. doi:10.1111/j.1398-9995.1988.tb02046.xAberer, W., Bircher, A., Romano, A., Blanca, M., Campi, P., … Fernandez, J. (2003). Drug provocation testing in the diagnosis of drug hypersensitivity reactions: general considerations. Allergy, 58(9), 854-863. doi:10.1034/j.1398-9995.2003.00279.xSALVO, F., POLIMENI, G., CUTRONEO, P., LEONE, R., CONFORTIC, A., MORETTI, U., … CAPUTI, A. (2008). Allergic reactions to oral drugs: A case/non-case study from an Italian spontaneous reporting database (GIF). Pharmacological Research, 58(3-4), 202-207. doi:10.1016/j.phrs.2008.07.003Blanca, M., Romano, A., Torres, M. J., Férnandez, J., Mayorga, C., Rodriguez, J., … Atanasković-Marković, M. (2009). Update on the evaluation of hypersensitivity reactions to betalactams. Allergy, 64(2), 183-193. doi:10.1111/j.1398-9995.2008.01924.xBircher, A. J., & Scherer Hofmeier, K. (2012). Drug hypersensitivity reactions: Inconsistency in the use of the classification of immediate and nonimmediate reactions. Journal of Allergy and Clinical Immunology, 129(1), 263-264. doi:10.1016/j.jaci.2011.08.042Terrados, S., Blanca, M., Garcia, J., Vega, J., Torres, M. J., Carmona, M. J., … Fernandez, J. (1995). Nonimmediate reactions to betalactams: prevalence and role of the different penicillins. Allergy, 50(7), 563-567. doi:10.1111/j.1398-9995.1995.tb01200.xGómez, E., Blanca-Lopez, N., Salas, M., Canto, G., Campo, P., Torres, M. J., … Blanca, M. (2013). Induction of accelerated reactions to amoxicillin by T-cell effector mechanisms. Annals of Allergy, Asthma & Immunology, 110(4), 267-273. doi:10.1016/j.anai.2013.01.003Blanca-López, N., Pérez-Sánchez, N., Agúndez, J. A., García-Martin, E., Torres, M. J., Cornejo-García, J. A., … Doña, I. (2016). Allergic Reactions to Metamizole: Immediate and Delayed Responses. International Archives of Allergy and Immunology, 169(4), 223-230. doi:10.1159/000444798Alonso, M. D., Martín, J. A., Quirce, S., Dávila, I., Lezaun, A., & Cano, M. S. (1993). Fixed eruption caused by ciprofloxacin with cross-sensitivity to norfloxacin. Allergy, 48(4), 296-297. doi:10.1111/j.1398-9995.1993.tb00733.xDavila, G., Ruiz-Hornillos, J., Rojas, P., De Castro, F., & Zubeldia, J. M. (2009). TOXIC EPIDERMAL NECROLYSIS INDUCED BY LEVOFLOXACIN. Annals of Allergy, Asthma & Immunology, 102(5), 441-442. doi:10.1016/s1081-1206(10)60521-2Ayllón, M. L., Martinez, M. G., Mosquera, M. R., Laguna Martinez, J. J., Martiartu, M. O., & Fernández de Miguel, C. (1995). Fixed eruption caused by ciprofloxacin without cross-sensitivity to norfloxacin. Allergy, 50(7), 598-599. doi:10.1111/j.1398-9995.1995.tb01206.xEmpedrad, R. (2003). Nonirritating intradermal skin test concentrations for commonly prescribed antibiotics. Journal of Allergy and Clinical Immunology, 112(3), 629-630. doi:10.1016/s0091-6749(03)01783-4Brož, P., Harr, T., Hecking, C., Grize, L., Scherer, K., Jaeger, K. A., & Bircher, A. J. (2012). Nonirritant intradermal skin test concentrations of ciprofloxacin, clarithromycin, and rifampicin. Allergy, 67(5), 647-652. doi:10.1111/j.1398-9995.2012.02807.xUyttebroek, A. P., Sabato, V., Bridts, C. H., De Clerck, L. S., & Ebo, D. G. (2015). Moxifloxacin hypersensitivity: Uselessness of skin testing. The Journal of Allergy and Clinical Immunology: In Practice, 3(3), 443-445. doi:10.1016/j.jaip.2014.12.012Fernandez-Rivas, M. (1997). Fixed drug eruption (FDE) caused by norfloxacin. Allergy, 52(4), 477-478. doi:10.1111/j.1398-9995.1997.tb01035.xChang, B., Knowles, S. R., & Weber, E. (2010). Immediate Hypersensitivity to Moxifloxacin with Tolerance to Ciprofloxacin: Report of Three Cases and Review of the Literature. Annals of Pharmacotherapy, 44(4), 740-745. doi:10.1345/aph.1m579Sánchez-Morillas, L., Rojas Pérez-Ezquerra, P., Reaño-Martos, M., Laguna-Martínez, J. J., & Gómez-Tembleque, P. (2010). Systemic anaphylaxis caused by moxifloxacin. Allergologia et Immunopathologia, 38(4), 226-227. doi:10.1016/j.aller.2009.09.00