Immunoglobulin E-mediated severe anaphylaxis to paclitaxel.

Immediate hypersensitivity reactions to taxanes have been related to nonspecifi c mediator release from mast cells. While the excipient macrogolglycerol ricinoleate has been implicated in complement or mast cell activation, an immunoglobulin (Ig) E-mediated mechanism has never been demonstrated. We report the case of a 49-year-old woman with a history of isocyanate-induced occupational asthma who presented with an enlarged supraclavicular lymph node identifi ed as a poorly differentiated adenocarcinoma. The patient was started on carboplatin and paclitaxel and tolerated the fi rst cycle well. During the second cycle, however, a few seconds after starting paclitaxel infusion, she presented dizziness, fl ushing, dyspnea, desaturation, hypotension, and collapse requiring orotracheal intubation. Carboplatin was not administered. Intravenous premedication with granisetron, ranitidine, methylprednisolone, products was performed using an IgE dot-blot assay (Bio-Rad, Hercules, California, USA) according to the manufacturer’s instructions, with 53 mg of paclitaxel reconstituted in 500 μL of dimethyl sulfoxide (Sigma-Aldrich, Madrid, Spain) and unmodifi ed macrogolglycerol ricinoleate. A polyvinylidene fluoride transfer membrane was used. Serum was applied with a blocking buffer (phosphate buffered saline containing 1% bovine serum albumin and 0.05% Tween, 1:1 v/v). The antibody was a mouse anti-human IgE (Fc) HRP (Southern Biotech) and the Western Lightning Plus-ECL system (PerkinElmer Life and Analytical Sciences, Shelton, Connecticut, USA) was used as substrate. The results were positive for paclitaxel and negative for macrogolglycerol ricinoleate (Figure). The patient was changed to an alternative chemotherapy regimen with cisplatin and gemcitabine, with good tolerance and complete response. Taxanes have been avoided. As a challenge test was not carried out with macrogolglycerol ricinoleate, the patient was instructed to avoid drugs containing this excipient (a list was supplied). Paclitaxel-related immediate hypersensitivity reactions occur in up to 30% of patients, with this percentage decreasing to under 10% with the administration of antihistamine and corticosteroid premedication [1-3]. Most reactions occur within the fi rst few minutes of infusion, usually after the fi rst or second dose, indicating that prior sensitization is not necessary. For this reason these reactions are thought to be non-IgE mediated [1-4]. Macrogolglycerol ricinoleate has also been implicated in anaphylactic reactions on the basis that it can induce complement activation, giving rise to anaphylotoxins that trigger mast cells and basophils for a secretory response [5]. The use of premedication and/or the slowing of infusion rates are effective but not always successful [6]. A safe and effective standardized protocol for rapid drug desensitization