Diagnostic workup including CD203c‐based basophil activation test in immediate hypersensitivity due to metronidazole and ornidazole and evaluation of cross‐reactivity in between

• Published in: Allergy (Copenhagen) Vol. 76; no. 3; pp. 842 - 852
• Main Authors: Beyaz, Şengül, Akdeniz, Nilgün, Yılmaz, Abdullah, Demir, Semra, Öztop, Nida, Çolakoğlu, Bahauddin, Büyüköztürk, Suna, Deniz, Günnur, Gelincik, Aslı
• Format: Journal Article
• Language: English
• Published: Denmark Blackwell Publishing Ltd 01.03.2021
• Subjects: 5‐Nitroimidazole antibiotics; Anaphylaxis; Angioedema; Antibiotics; basophil activation test; Basophil Degranulation Test; Basophils; Drug Hypersensitivity - diagnosis; Drugs; Humans; Hypersensitivity (immediate); Hypersensitivity, Immediate - chemically induced; Hypersensitivity, Immediate - diagnosis; immediate drug hypersensitivity reactions; Medical diagnosis; Metronidazole; Metronidazole - adverse effects; Nitroimidazole; Ornidazole; Ornidazole - adverse effects; Placebos; Provocation tests; Single-Blind Method; Skin Tests; Urticaria; basophil activation test; immediate drug hypersensitivity reactions; metronidazole; ornidazole; 5-Nitroimidazole antibiotics
• ISSN: 0105-4538; 1398-9995; 1398-9995
• DOI: 10.1111/all.14542

Background Little is known about the diagnostic approaches for immediate hypersensitivity reactions (IHRs) due to 5‐nitroimidazole antibiotics. The aim was to evaluate the usefulness of in vivo tests and basophil activation test (BAT) for the diagnosis of IHRs due to metronidazole and ornidazole and to determine possible cross‐reactivity in between. Methods Forty‐nine patients with a clear history of IHRs due to these drugs and 20 healthy subjects who were known to tolerate these drugs were included. Skin tests (STs) and single‐blind placebo‐controlled drug provocation tests (SBPCDPTs) were performed with both drugs whereas BAT was applied only with the culprit drug. Results The most and least common reaction types were urticaria/angioedema (34.7%) and anaphylaxis (14.3%), respectively. SBPCDPTs were positive in 15 out of 47 patients, and only 7 had positive STs. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of STs for metronidazole/ornidazole were 33.3%/16.6%, 94.2%/97.3%, 60%/50%, and 84.6%/88.1%, respectively. BAT was positive in 12 out of 15 patients and negative in 10 control subjects, giving a sensitivity rate of 71.4% (CI, 29.0%‐96.3%) for metronidazole and 83.3% (CI, 35.8%‐99.5%) for ornidazole. The optimal concentration of both drugs for BAT was determined as 5 mg/mL. No cross‐reactivity among two drugs was observed according to in vivo tests. Conclusions Our study showed that SBPCDPT and BAT are both useful diagnostic tools for IHRs due to 5‐nitroimidazole antibiotics and can be used as supplementary to each other. No cross‐reactivity between metronidazole and ornidazole in IHRs exists. Forty‐nine patients with immediate hypersensitivity reaction (IHRs) due to 5‐nitroimidazole antibiotics (metronidazole and ornidazole) and 20 control subjects are evaluated. Overall 14.5% and 80% reveal positive ST results and basophil activation test (BAT) results, respectively. Sensitivity, specificity, and negative predictive value (NPV) of skin test (STs) for metronidazole/ornidazole are 33.3%/16.6%, 94.2%/97.3%, and 84.6%/88.1%, respectively. Sensitivity, specificity, and NPV of BAT for metronidazole/ornidazole are 71.4%/83.3%, 100%/100%, and 71.4%/83.3%, respectively. Abbreviations: BAT, basophil activation test; IHR, immediate hypersensitivity reaction; NPV, negative predictive value; ST, skin test.