A 55-year-old woman without prior history of drug allergy, scheduled for cataract surgery, received oral levofloxacin (500mg) for antibiotic prophylaxis. Within minutes after levofloxacin intake, she experienced sneezing and palmoplantar pruritus followed by generalised pruritus along with facial, lingual and pharyngeal angio-oedema and subsequent dyspnoea. These clinical signs were followed by digestive (i.e. vomiting, abdominal pain and diarrhoea) and cutaneous (generalised erythema) signs. Surgery was postponed. Clinical signs resolved within hours with hydrocortisone and dexchlorpheniramine. Further clinical outcome was uneventful.
Plasma histamine (70nmoll−1, N<10) and serum tryptase (32.7μgl−1, N<13.5) measured 75min after the clinical reaction, showed increased concentrations. Basal tryptase (3.4μgl−1) measured two days after remained unchanged. With the patient's consent, allergological assessment was performed four weeks later. Prick-test (PT) at 10−2 dilution (0.05mg/ml) was positive in response to levofloxacin. Cross-reactivity was found with ofloxacin through PT (10−1 dilution: 0.5mg/ml) while skin testing remained negative in response to ciprofloxacin (i.e. PT stock solution: 2mg/ml and intradermal tests up to 10−1 dilution: 0.2mg/ml). Pefloxacin was not skin-tested. IgE-mediated levofloxacin-induced allergy, with cross-reactivity to ofloxacin and absence of cross-reactivity to ciprofloxacin, was therefore confirmed on the basis of the typical clinical history, increased tryptase level along with skin test results. With the patient's informed consent and under medical supervision, graded drug challenge using ciprofloxacin at increasing intravenous doses (cumulative dose: 150mg) was performed1 and remained negative, therefore excluding ciprofloxacin sensitisation.
Although rare, immediate hypersensitivity to quinolones may be due to direct pharmacological effects (i.e. histamine release) or IgE-mediated mechanism.2,3 Ciprofloxacin is frequently involved as it is the most commonly quinolone used.3 The diagnostic values of skin tests in quinolone allergy remain controversial. Contradictory results regarding the sensitivity of skin tests in quinolone allergy have been reported, whereas in controls, positive skin tests were attributed to direct mast cell activation.4 Thus, low non-irritating intradermal tests concentrations for quinolones were proposed with subsequent low sensitivity of intradermal tests to these drugs.4 Others suggest using specific Sepharose-RIA assay to prove quinolone IgE-mediated hypersensitivity.3 However, a few in vitro studies showed that the sensitivity of the RIA-assay and the basophil activation test differed according to the fluoroquinolone tested5 while these results3,5 were, in the meantime, not compared to the in vivo skin tests results.
Fluoroquinolones are synthetic derivatives of nalidixic acid with a common core of a bicyclic ring structure and cross-reactivity, related to the structure of the molecules, seems to be common.3,4 Our patient showed cross-reactivity to ofloxacin as levofloxacin is the active L-isomer of ofloxacin. Both are fluorinated 4-quinolones containing a pyridobenzoxazine ring from positions 1 to 8 of the basic ring structure. Side chain reactivity to these sites alone might explain cross-reactivity to ofloxacin and lack of cross-reactivity to ciprofloxacin, as ciprofloxacin is devoided of any side chain in this position.2 However, there is no general rule to predict cross-reactivity between quinolones. Thus to be complete during the diagnostic approach of quinolone-induced IgE-mediated anaphylaxis, investigation for cross-reactivity with the other commercialised quinolones should be performed in order to identify safe alternative regimens (i.e. negative skin-tested quinolones).
Intravenous challenge with ciprofloxacin remained uneventful and thus excluded cross-reactivity with related drugs (i.e. levofloxacin and ofloxacin). This allowed providing a safe alternative in cases of fluoroquinolones requirement in our patient. This finding contrasts with other reports suggesting strict avoidance of all quinolones in patients with quinolone-allergy.3,6
In conclusion, skin test might be a useful tool to prove quinolone-induced IgE-mediated hypersensitivity, whereas the challenge test might help to confirm the negative predictive values of skin tests to quinolones and thus authorise a safe alternative.
FundingSupport was solely provided from institutional and/or departmental resources.
Ethical disclosuresProtection of human and animal subjectsThe authors declare that no experiments were performed on humans for this investigation.
Confidentiality of dataThe authors declare that no patient data appears in this article.
Right to privacy and informed consentThe authors declare that no patient data appears in this article.
