Minocycline-induced anaphylaxis mediated by antigen-specific immunoglobulin E.

Abstract

Drug-induced anaphylaxis can be caused by mechanisms that do not essentially involve immunoglobulin (Ig)E. Minocycline has been reported to occasionally cause anaphylaxis. However, whether this reaction is mediated by IgE remains unclear.1, 2 Herein, we report a case of minocycline-induced anaphylaxis with antigen-specific IgE. A 67-year-old woman was treated for common cold with minocycline, an antitussive medication containing codeine phosphate hydrate, and an anti-flatulent. Thirty minutes after receiving the medications orally, she developed generalized erythema and dyspnea. These symptoms rapidly improved with the administration of i.m. epinephrine and supplemental fluids. She had taken minocycline twice in the past and had experienced dizziness immediately after the second dose. However, she did not develop any adverse effects to the antitussive medication on the past several occasions. Skin prick tests showed a positive response for minocycline (0.5 mg/mL) and codeine phosphate hydrate (10 mg/mL), with wheal sizes of 3.5 mm and 3.0 mm, respectively. Based on previous literature, a wheal diameter of 3 mm or more was considered positive.3 Skin prick tests for all the other drugs consumed before the appearance of anaphylactic symptoms were negative. We then performed a histamine release test (HRT) by a previously described method using basophils from the patient.4 No histamine release was observed in response to these drugs in the absence of autologous serum. However, minocycline caused a concentration-dependent release of histamine in the presence of the patient’s serum (Figure 1a). In contrast, histamine was only marginally released following the stimulation of basophils with 1% codeine phosphate hydrate (Figure 1a), leading to the diagnosis of minocycline-induced anaphylaxis. With the autologous serum, basophils from three healthy controls did not release histamine in response to minocycline (Figure S1). The dot blot assay, performed according to a previously described method,4 revealed the specific binding of IgE to minocycline in the presence of the patient’s serum (Figure 1b). However, IgE in the patient’s serum did not show any specific binding to codeine phosphate (data not shown). She then took codeine phosphate hydrate and did not show any allergic symptoms. Informed consent was obtained from the patient for the publication of her clinical and laboratory data. Several cases of hypersensitivity reactions to minocycline have been reported.2, 3, 5 However, they identified minocycline as the cause of immediate allergy/anaphylaxis based on the results of skin and oral challenge tests.2, 3 Although these tests can confirm an individual’s hypersensitivity to minocycline, they cannot determine whether the reaction was mediated by antigen-specific IgE and histamine. In our case, the HRT showed that minocycline elicited no response from basophils in the absence of autologous serum. Owing to its small molecular weight 493.94, minocycline cannot directly cross-link multiple IgE antibodies, which may partially explain why the patient’s basophils did not respond to minocycline in the absence of serum (Figure 1a). In this case, basophils released histamine upon stimulation with minocycline in the presence of autologous serum, suggesting the presence of minocycline–haptic carrier proteins in the patient’s serum. In conclusion, this report indicates that minocycline can cause IgE-mediated type I allergic reactions. None. None declared. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.