In Vitro Diagnosis of Immediate Drug Hypersensitivity Anno 2017: Potentials and Limitations

Abstract

BackgroundFor most physicians, quantification of drug-specific immunoglobulin E (drug-sIgE) antibodies constitutes the primary in vitro measure to document immediate drug hypersensitivity reactions (IDHR). Unfortunately, this is often insufficient to correctly identify patients with IgE-mediated IDHR and impossible for non-IgE-mediated IDHR that result from alternative routes of basophil and mast cell activation. In these difficult cases, diagnosis might benefit from cellular tests such as basophil activation tests (BAT).AimThe aim was to review the potential and limitations of quantification of sIgE and BAT in diagnosing IDHR. The utility of quantification of serum tryptase is discussed.MethodsA literature search was conducted using the key words allergy, basophil activation, CD63, CD203c, diagnosis, drugs, hypersensitivity, flow cytometry, specific IgE antibodies; this was complemented by the authors’ own experience.ResultsThe drugs that have been most studied with both techniques are β-lactam antibiotics and curarizing neuromuscular blocking agents (NMBA). For sIgE morphine, data are available on the value of this test as a biomarker for sensitization to substituted ammonium structures that constitute the major epitope of NMBA, especially rocuronium and suxamethonium. For the BAT, there are also data on non-steroidal anti-inflammatory drugs (NSAIDs) and iodinated radiocontrast media. For β-lactam antibiotics, sensitivity and specificity of sIgE varies between 0 and 85% and 52 and 100%, respectively. For NMBA, sensitivity and specificity varies between 38.5 and 92% and 85.7 and 100%, respectively. Specific IgE to morphine should not be used in isolation to diagnose IDHR to NMBA nor opiates. For the BAT, sensitivity generally varies between 50 and 60%, whereas specificity attains 80%, except for quinolones and NSAIDs.ConclusionsAlthough drug-sIgE assays and BAT can provide useful information in the diagnosis of IDHR, their predictive value is not absolute. Large-scale collaborative studies are mandatory to harmonize and optimize test protocols and to establish drug-specific decision thresholds.

Neuromuscular blocking agents induced anaphylaxis: Results and trends of a French pharmacovigilance survey from 2000 to 2012

“…Skin testing involves the incriminated NMBA but also the other available NMBAs in order to detect cross‐reactivity and to provide recommendations on the safe use of other NMBA(s) for future anesthesia . In vitro tests remain discussed, as specific IgE (sIgE) to morphine (c260 ImmunoCAP ® ‐Phadia) or to SUX (c202 ImmunoCAP(R°‐Phadia) lack specificity, whereas basophil activation tests lack of sensitivity and validated decision thresholds . However, in cases with fatal outcome with a typical clinical presentation and increased tryptase, positive sIgE are sometimes the only test to give a trend to the diagnosis.…”

Rocuronium anaphylaxis in a 7-year-old boy during the induction of anesthesia

“…In January 2018, Japan Medical Safety Research Organization announced that rocuronium had induced two out of 12 anaphylaxis deaths after injection of drugs in adult cases. Given the current situation, rocuronium is contraindicated and we should plan skin tests and if possible, in combination with basophil activation test to several NMBA [12] before an elective surgery in our case. Additionally, under the necessity of using propofol and cefazolin sodium, we need to consider indication, drip speed, and doses.…”

Occupational generalized urticaria and anaphylaxis after inhalation of cefuroxime in a nurse

“…Sensitivity and specificity of specific IgE testing for β‐lactam antibiotics vary between 0 and 85%, and 52 and 100%, respectively . Overall, specificity of specific IgE testing has consistently been reported as being higher than sensitivity .…”