100440 - Oxycodone/naloxone-induced anaphylactic shock with naloxone as the most likely culprit: diagnostic contribution of the basophil activation test

Background: Hypersensitivity reactions to opioids are common, but true IgE-mediated allergies are rare. Most reactions are non-immunological, resulting from direct mast cell degranulation. The fixed-dose combination of oxycodone/naloxone is widely used for chronic pain. Anaphylaxis to this combination is typically attributed to the opioid component, oxycodone. We present a case of anaphylactic shock where the causative agent was identified as naloxone, the opioid antagonist, challenging initial assumptions.

Methods: A 79-year-old woman, previously tolerant to tramadol, developed anaphylactic shock (hypotension 63/42 mmHg, bradycardia, generalized rash, mixed acidosis) shortly after the second oral dose of oxycodone/naloxone. Serum tryptase was measured during the event and at baseline. Skin prick and intradermal tests were performed with oxycodone and naloxone using non-irritant dilutions. A basophil activation test (BAT) by flow cytometry (CD63) was carried out for both drugs. KIT D816V testing in peripheral blood was used to assess clonal mast cell disease.

Results: Tryptase peaked at 44.9 ug/L 4–5 h after onset and decreased to 19.6 ug/L at 24 h, with a normal baseline. In the intensive care unit (ICU), the patient tolerated morphine, fentanyl and remifentanil. Skin tests were negative to both drugs. BAT was positive to naloxone at two dilutions (6.8% and 7.2% CD63+ basophils; positivity threshold >5%) and negative to oxycodone (1.3% and 2.4%). Baseline tryptase and KIT D816V were normal/negative.

Conclusions: Findings support immune-mediated hypersensitivity to naloxone, a rarely suspected component of oxycodone/naloxone. When skin testing is negative or inconclusive, BAT may help identify the culprit drug and avoid unnecessary avoidance of alternative opioids. Written informed consent was obtained.