A.L. Van Gasse

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.

Allergy to illicit drugs and narcotics

Despite their frequent use, allergy to illicit drugs and narcotics is rarely reported in literature. We present a review of the different classes of drugs of abuse that might be involved in allergies: central nervous system (CNS) depressants (such as cannabis, opioids and kava), CNS stimulants (cocaine, amphetamines, khat and ephedra) and hallucinogens such as ketamine and nutmeg. Diagnosis of drug and narcotic allergy generally relies upon careful history taking, complemented with skin testing eventually along with quantification of sIgE. However, for various reasons, correct diagnosis of most of these drug allergies is not straightforward. For example, the native plant material applied for skin testing and sIgE antibody tests might harbour irrelevant IgE‐binding structures that hamper correct diagnosis. Diagnosis might also be hampered due to uncertainties associated with the non‐specific histamine releasing characteristics of some compounds and absence of validated sIgE tests. Whether the introduction of standardized allergen components and more functional tests, that is, basophil activation and degranulation assays, might be helpful to an improved diagnosis needs to be established. It is anticipated that due to the rare character of these allergies further validation is although necessary.

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

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.

Cannabis sativa allergy: looking through the fog.

IgE‐mediated Cannabis (C. sativa, marihuana) allergy seems to be on the rise. Both active and passive exposure to cannabis allergens may trigger a C. sativa sensitization and/or allergy. The clinical presentation of a C. sativa allergy varies from mild to life‐threatening reactions and often seems to depend on the route of exposure. In addition, sensitization to cannabis allergens can result in various cross‐allergies, mostly for plant foods. This clinical entity, designated as the ‘cannabis‐fruit/vegetable syndrome’, might also imply cross‐reactivity with tobacco, natural latex and plant‐food‐derived alcoholic beverages. Hitherto, these cross‐allergies are predominantly reported in Europe and appear mainly to rely upon cross‐reactivity between nonspecific lipid transfer proteins or thaumatin‐like proteins present in C. sativa and their homologues, ubiquitously distributed throughout plant kingdom. At present, diagnosis of cannabis‐related allergies predominantly rests upon a thorough history completed with skin testing using native extracts from crushed buds and leaves. However, quantification of specific IgE antibodies and basophil activation tests can also be helpful to establish correct diagnosis. In the absence of a cure, treatment comprises absolute avoidance measures. Whether avoidance of further use will halt the extension of related cross‐allergies remains uncertain.

Immediate moxifloxacin hypersensitivity: Is there more than currently meets the eye?

Immediate drug hypersensitivity reactions (IDHR) to moxifloxacin constitute a pathomechanistic conundrum and a diagnostic challenge. Our objective was to study whether simultaneous phenotyping and quantification of histamine release might add to our knowledge about the basophil activation properties of moxifloxacin and constitute a reliable diagnostic aid. Fifteen patients with an IDHR to moxifloxacin and nine moxifloxacin challenged controls were selected. All had a basophil activation test (BAT) with moxifloxacin. Flow cytometric analysis of basophil responses implied labeling for CD63, CD203c, and intracellular histamine. Unlike tolerant challenged controls, basophilic upregulation of CD203c in response to moxifloxacin was observed in seven of 15 patients. Only two of these seven patients demonstrated appearance of CD63 and release of histamine. In the remainder eight patients, no basophil responses were demonstrable. In conclusion, immediate hypersensitivity to moxifloxacin might involve mechanisms difficult to capture by traditional CD63‐/CD203c‐based BAT. Deciphering the complexity of quinolone IDHR seems mandatory.

Basophil Activation Test in IgE-Mediated Food Allergy: Should We Follow the Flow?

Opinion statementIgE-mediated food allergy constitutes an important and increasing health issue with significant impairment of quality of life and significant morbidity and mortality. It affects children, as well as adolescents, and adults. Correct diagnosis of food allergy relies upon history supplemented by quantification of specific IgE (sIgE) antibodies and/or skin tests. Unfortunately, as these tests do not demonstrate absolute predictive values, controlled oral provocation tests might be needed to confirm/exclude diagnosis. However, it is unlikely oral challenges to enter mainstream application, mainly because of obvious ethical reasons. Therefore, correct diagnosis of food allergy might benefit from novel in vitro diagnostics such as allergen component-based sIgE assays and flow cytometric quantification of in vitro activated basophils. As a matter of fact, these tests might prove to be particularly helpful in discriminating genuine allergy from merely sensitization. Furthermore, they might be useful in establishing individual risk profiles, predicting persistence of allergy, and facilitating therapeutic approach. This review focuses on the applications and limitations of the basophil activation test in IgE-mediated food allergy. Anno 2016 we believe that the utility and usefulness of basophil-activation experiments need to be reevaluated thoroughly, in view of difficulties inherent to the correct preparation and storage of allergen extracts, optimizing and standardizing stimulation conditions, and also the potential of alternative diagnostics such as component resolved diagnosis that are becoming more readily accessible.

Cannabis allergy: A diagnostic challenge

M. Saito K. Yamamoto-Hanada K. Pak T. Ayabe H. Mezawa K. Ishitsuka M. Konishi L. Yang K. Matsumoto H. Saito Y. Ohya The Japan Environment and Children’s Study (JECS) Group Medical Support Center for the Japan Environment and Children’s Study, National Center for Child Health and Development, Tokyo, Japan Department of Clinical Medicine (Biostatistics), Kitasato University School of Pharmacy, Tokyo, Japan Email: yamamoto-k@ncchd.go.jp

Cannabis Allergy: More Than a Bad Trip

Abstract Cannabis allergy seems to be an increasing problem in the past few years. Both active and passive exposure to cannabis allergens may lead to a cannabis sensitization and/or allergy. The clinical manifestations can vary from mild to life-threatening reactions, often depending on the route of exposure. Sensitization to cannabis can lead to secondary cross-allergies, such as plant-derived food allergies, which we have designated as the “cannabis-fruit/vegetable syndrome.” These secondary cross-allergies are mostly described in Europe, and result from cross-reactivity between nonspecific lipid transfer proteins (ns-LTPs) or thaumatin-like proteins (TLPs) present in Cannabis sativa and their homologs. At present, diagnosis of cannabis-related allergies rests upon history, skin testing, IgE-testing, and a basophil activation test. Treatment comprises strict avoidance measures, including an absolute stop of cannabis abuse.