Morphine and pholcodine-specific IgE have limited utility in the diagnosis of anaphylaxis to benzylisoquinolines

Acta Anaesthesiol Scand. 2018 May;62(5):628-634. doi: 10.1111/aas.13077. Epub 2018 Jan 24.

Abstract

Background: Investigation of immediate hypersensitivity reactions in the perioperative setting involves skin testing and measurement of specific IgE (sIgE) as standard practice. In the case of the neuromuscular blocking agents (NMBAs), the main allergenic epitopes have been shown to be substituted ammonium groups. Commercial assays are available for detection of sIgE to these epitopes using morphine and pholcodine substrates but questions have been raised about the effectiveness of these assays in the diagnosis of benzylisoquinoline anaphylaxis. This study was therefore undertaken to assess the effectiveness of these assays in the diagnosis of hypersensitivity reactions to this group of NMBAs.

Methods: Analysis was carried out on all available results for patients assessed at the Royal North Shore Hospital Anaesthetic Allergy Clinic during the period June 2009 to June 2016. Standardised intradermal skin tests were performed with a panel of NMBAs. Measurement of sIgE to morphine and pholcodine was performed via the Phadia ImmunoCAP® system.

Results: For all patients with positive skin test results to NMBAs which included a benzylisoquinoline NMBA (n = 24), 75% exhibited negative sIgE to both morphine and pholcodine. Where patients were reactive to benzylisoquinoline NMBAs alone (n = 12), 100% exhibited negative sIgE results, indicating 0% sensitivity of the assays relative to skin testing, in this subgroup.

Conclusion: Use of sIgE testing to morphine and pholcodine in the assessment of NMBA immediate hypersensitivity is a valuable tool particularly in the case of reactions to the aminosteroid NMBAs. However, these assays are unreliable in detecting sensitisation to benzylisoquinoline NMBAs.

MeSH terms

  • Anaphylaxis / diagnosis*
  • Benzylisoquinolines / adverse effects*
  • Codeine / analogs & derivatives*
  • Codeine / immunology
  • Drug Hypersensitivity / diagnosis*
  • Female
  • Humans
  • Immunoglobulin E / blood*
  • Male
  • Morphine / immunology*
  • Morpholines / immunology*
  • Neuromuscular Blocking Agents / adverse effects*
  • Skin Tests

Substances

  • Benzylisoquinolines
  • Morpholines
  • Neuromuscular Blocking Agents
  • Immunoglobulin E
  • Morphine
  • pholcodine
  • Codeine