What is known about immediate hypersensitivity reactions triggered by moxifloxacin?
A patient who previously suffered from a suspected immediate hypersensitivity reaction during treatment with moxifloxacin is again indicated for treatment with a fluoroquinolone.
The fluoroquinolones can trigger both immediate and delayed hypersensitivity reactions [1, 2]. Moxifloxacin is reported to be the fluoroquinolone most often associated with immediate hypersensitivity reactions and anaphylaxis . It differs from other fluoroquinolones by a methoxy group on carbon atom 8 .
In treatment with fluoroquinolones, the immediate reactions are most common. They typically occur within an hour of administration  and have been made up of anaphylaxis (62.5–64.3 percent), urticaria (30.4–35.7 percent), and angioedema (7.1 percent) . Anaphylaxis has also been described to occur in connection with the first exposure .
The immediate reactions upon exposure to fluoroquinolones can consist of both IgE-mediated and non-IgE-mediated reactions [1, 2]. In immediate hypersensitivity reactions to quinolones, IgE antibodies to quinolones are reported to have been detected in 30–55 percent of patients . An as yet unconfirmed hypothetical mechanism for reactions at first exposure has been prior sensitization to quaternary ammonium compounds . Non-IgE-mediated mast cell activation is another likely explanation. Fluoroquinolones can, like for example vancomycin, activate mast cells, and perhaps also basophils and eosinophils, via the mast cell receptor MRGPRX2 (Mas-related G-protein-coupled receptor X2) [1, 2].
Prick test and intradermal test. The value of skin testing is still debated. Sensitivity and specificity vary between different studies [1, 2]. It could be because the studied reactions had different mechanisms. Both dot test and intradermal test methodology are described [1, 2, 4, 5].
Provocation. Doses used for provocation are published . If the patient previously had a severe reaction to a quinolone, provocation with the triggering quinolone is considered contraindicated . Provocation with skin test-positive quinolones should also be avoided .
Cross sensitization. Cross-sensitisation/cross-reactivity is also a partly controversial issue. It has been suggested that a high risk of cross-reactivity would exist between first-generation quinolones, such as nalidixic acid, and second-generation (norfloxacin, ciprofloxacin) . The lowest risk of cross-reactivity appears to be with levofloxacin, which belongs to the third generation quinolones . In case of suspected allergy to moxifloxacin, a quinolone in the fourth generation, it has been suggested that provocation could be carried out with a quinolone from the first generation or, for example, levofloxacin from the third generation .
A patient who had anaphylaxis when exposed to moxifloxacin and had a positive intradermal test with moxifloxacin then had negative skin tests and negative oral provocation with levofloxacin . In another publication, it is described that three patients with reactions to oral moxifloxacin later tolerated ciprofloxacin . However, they did not have positive intradermal tests against moxifloxacin .
Desensibilisering. If there is a strong indication for re-exposure, administration with a desensitization procedure may also be an option [2, 8].
Summary. Moxifloxacin and other fluoroquinolones are considered to be able to cause immediate hypersensitivity reactions already upon first exposure. Both IgE-mediated reactions and direct mast cell activation, for example via the MRGPRX2 receptor, have been described. Moxifloxacin is the fluoroquinolone most often prescribed in connection with anaphylaxis. Skin tests should be considered before deciding on provocation. The cross-sensitization/cross-reactivity pattern is incompletely known. For an individual who has previously reacted to moxifloxacin, levofloxacin has been considered to carry the lowest risk upon provocation. Desensitization may be considered.
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