Immediate hypersensitivity reactions to quinolones are not common in frequency from 0.4% to 2%.4,5
A literature review revealed that ciprofloxacin was the most frequently implicated because of its high consumption, followed by ofloxacin and cinoxacin. The most frequent reactions were urticaria and anaphylaxis.6,7
In this study, we report the clinical features of five patients with ofloxacin hypersensitivity compared to five with ciprofloxacin hypersensitivity by detection of serum-specific IgE antibodies.
As a method of diagnosis of quinolone hypersensitivity, skin test results have been contradictory and unreliable,8
giving false positive responses in healthy controls by inducing direct histamine release.6,9
In this study, all group I subjects exhibited negative SPT results to the maximum ofloxacin concentration. A few studies have reported the presence of serum-specific IgE to ciprofloxacin and moxifloxacin using radioimmunoassay,6,10
however, the method has a risk of radiation exposure. The present study, to the best of our knowledge, is the first to demonstrate a high positive rate (80%) of serum-specific IgE to ofloxacin-HSA conjugate using ELISA, and to confirm IgE binding specificity by ELISA inhibition tests. Although the drug challenge test is the confirmative diagnostic method, it is not sufficiently risk-free to be performed in daily practice. The basophil activation test has been suggested as an alternative in vitro
test of quinolone hypersensitivity, however, the sensitivity ranges from 0%4
Based on these findings, measurement of serum-specific IgE to ofloxacin-HSA conjugate using ELISA may be a useful and reliable in vitro
method for diagnosing ofloxacin hypersensitivity, obviating the need for challenge tests.
The basic structure of quinolones is a nitrogen-containing eight-member heterocyclic aromatic compound with a carboxylic group at position 3 and a ketone group at position 4. The addition of a fluorine substituent at position 6 and a piperazinyl moiety at position 7 resulted in ciprofloxacin and the addition of a methyl substituent on the piperazine ring led to ofloxacin. IgE antibodies interact mainly with the side chains at positions 2-6,7
and frequent cross reactivity among structurally similar quinolones has been suggested.4,12,13
In this study, three (60%) group II subjects had high serum-specific IgE to ofloxacin-HSA conjugate, and they showed significant inhibition with additions of both ofloxacin and ofloxacin-HSA conjugate (data not shown). Of the group I subjects having high serum-specific IgE to ofloxacin-HSA conjugate, significant inhibitions were noted with the free forms of ciprofloxacin and ofloxacin in patient 3, whereas only minimal inhibitions were noted with free ciprofloxacin in patient 1, indicating that ofloxacin has immunologic cross reactivity with ciprofloxacin, which differ between individuals. These data suggest the utility of ELISA and ELISA inhibition testing for evaluating cross reactions with structurally similar quinolones in patients with ofloxacin hypersensitivity.
Few studies have investigated the role of specific IgG in antibiotics allergies.9
In this study, some group I and II subjects had high specific IgG4 levels, suggesting a parallel immune response with specific IgE, but without a pathologic role.
In conclusion, we suggest that an IgE-mediated response to the hapten part of ofloxacin is the major pathogenic mechanism underlying ofloxacin hypersensitivity. In addition, cross reactivity with ciprofloxacin was noted, although this differed between individual subjects.