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

BACKGROUND: For 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). AIM: The 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. METHODS: A 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. RESULTS: The drugs that have been most studied with both techniques are ß-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 ß-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. CONCLUSIONS: Although 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.

Flow-assisted basophil activation tests in immediate drug hypersensitivity: two decades of Antwerp experience.

The last two decades have witnessed that flow-assisted analysis of in vitro-activated basophils can constitute a valuable adjunct in the in vitro diagnostic approach of immediate drug hypersensitivity reactions (IDHR). This article summarises the current experience with the basophil activation test in the diagnosis of IDHR, with particular focus on allergy to curarising neuromuscular blocking agents, antibiotics (ß-lactams and fluoroquinolones), iodinated radiocontrast media and opiates.

Molecular allergy diagnosis: status anno 2015.

IgE antibodies play a key role in type I allergic reactions. Today, different in vitro immunoassays for allergen-specific IgE antibodies are available. However, some major issues should be taken into account for correct interpretation of specific IgE (sIgE) antibody results, as these assays do not demonstrate absolute positive and negative predictive values. Therefore, additional diagnostic tests are needed to make the correct diagnosis. During the last two decades significant progress in biochemistry and molecular biology enabled the detection and quantification of sIgE antibodies to allergen protein components and epitope-emulating peptides, also called molecular allergy diagnosis or component resolved diagnosis (CRD). In contrast to conventional sIgE antibody assays, molecular allergy diagnosis makes it possible to discriminate between genuine allergy and merely sensitisation, to establish personalized sensitization patterns and to assess the individual risk of severity of an allergic reaction and finally it helps us to predict the natural course. In this review the use of CRD in inhalant, food, latex and hymenoptera venom allergy will be discussed. The primary focus will be on the most relevant clinical applications of CRD rather than to describe all the currently available allergen components and epitopes. Appropriate experience of our own research group is provided.