V. Sabato

New Food Allergies in a European Non-Mediterranean Region: Is Cannabis sativa to Blame?

Background: Allergy to fruit and vegetables exhibit geographic variation regarding the severity of symptoms and depending on the sensitization profile of the patient. These sensitization profiles and routes remain incompletely understood. Cannabis is a very popular drug and derived from Cannabis sativa, a plant containing lipid transfer proteins (LTP) also known as important allergens in plant and fruit allergies. In this study we sought to elucidate a potential connection between C. sativa allergy and plant food allergies. Methods: A case-control study involving 21 patients consulting for plant food allergies. Twelve patients were cannabis allergic and 9 had a pollen or latex allergy without cannabis allergy. Testing for cannabis IgE implied measurement of specific IgE, skin testing and basophil activation tests. Allergen component analysis was performed with a microarray technique. Results: Plant food allergy in patients with documented cannabis allergy had more severe reactions than patients without cannabis allergy and frequently implied fruits and vegetables that are not observed in a (birch) pollen-related food syndrome. With the exception of 1 patient with cannabis allergy, all were sensitized to nonspecific (ns)-LTP. Conclusion: Our data suggest that illicit cannabis abuse can result in cannabis allergy with sensitization to ns-LTP. This sensitization might result in various plant-food allergies. Additional collaborative studies in different geographical areas are needed to further elucidate on this hypothesis.

IgE-mediated allergy to pholcodine and cross-reactivity to neuromuscular blocking agents : lessons from flow cytometry

Immunoglubulin E antibody‐mediated allergic reactions to opioids are rare and difficult to document correctly.

Basophil activation tests: time for a reconsideration

Challenges in in vitro allergy diagnostics lie in the development of accessible and reliable assays allowing identification of all offending allergens and cross-reactive structures. Flow-assisted analysis and quantification of in vitro activated basophils serves as a diagnostic instrument with increasing applications developed over the years. From the earliest days it was clear that the test could constitute a diagnostic asset in basophil-mediated hypersensitivity. However, utility of the basophil activation test should be reassessed regarding difficulties with preparation, characterization and validation of allergen extracts; availability and the potential of more accessible diagnostics. Today, the added value mainly lies in diagnosis of immediate drug hypersensitivity. Other potential indications are monitoring venom-immunotherapy and follow-up of natural history of food allergies. However, results in these nondiagnostic applications are preliminary. We review the most relevant clinical applications of the basophil activation test. Some personal comments and views about perspectives and challenges about flow-assisted allergy diagnosis are made.

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.

Moxifloxacin hypersensitivity: Uselessness of skin testing

Quinolones are synthetic antibiotics based on the 4-quinolone and 1,8-naphthyridine nuclei. They can cause severe hypersensitivity reactions, even after first exposure, with moxifloxacin being an important culprit. Unfortunately, a diagnosis of quinolone hypersensitivity is not straightforward, because of the absence of drug-specific sIgE immunoassays and uncertainties associated with skin testing with potentially nonspecific histamine releasers. These contradictory studies show that establishing nonirritating skin-test concentrations for ciprofloxacin is not straightforward. For example, Broz et al recommend an intradermal test (IDT) concentration of 1:300 to 1:1000 in saline for ciprofloxacin. In contrast, the Empedrad study failed to determine a nonirritating concentration for ciprofloxacin because the irritating concentration varied a 1000-fold in healthy volunteers. Accordingly, the European Network on Drug Allergy and European Academy of Allergy and Clinical ImmunologyDrugAllergy InterestGrouphasmadenodrugspecific recommendations about skin prick test (SPT) and/or IDT with quinolones. For moxifloxacin, the literature reveals “nonirritant” concentrations for SPT to vary between 1 and 20 mg/mL and for IDT between 0.004 and 0.05 mg/mL. However, inspection of the data discloses that 3/5 studies did not include controls and data gathered in patients were restricted to a maximum of 5 cases. This study assessed SPT and IDT in the diagnosis of immediate moxifloxacin hypersensitivity. A comparative study was performed between patients with histories of reactions and controls who tolerated a graded oral drug provocation test (DPT) with moxifloxacin. Patient inclusion was based on clinical history. Fourteen patients with a history of an immediate hypersensitivity reaction to moxifloxacin were enrolled. All patients suffered from urticaria/angioedema, bronchospasm/hypotension, and/or loss of consciousness within 60 minutes after intake. Other possible causes were excluded (ie, concomitant intake of other drugs). Time between reaction and investigation ranged between 0.3 and 21 months (median: 4 months) (Table I). Sixteen individuals who tolerated a graded oral DPT served as an exposed-control group. Skin testing consisted of SPTs and IDTs with a parenteral formulation ofmoxifloxacin hydrochloride (Avelox 400mg/250mL [or 1.6 mg/mL], Bayer SA-NV, Diegem, Belgium). SPT was performed using a 1:10 dilution and undilutedmoxifloxacin. Results were considered positive when wheal/flare equaled or exceeded 3/3 mm. For IDTs, serial dilutions of 1:1000, 1:100, and 1:10 were used. Results were considered positive when the wheal equaled or exceeded 5 mm. Patients with a history of betalactam hypersensitivity are more prone to develop hypersensitivity reactions to fluoroquinolones. Because the majority of subjects included as controls consulted with such a history, we preferred a graded DPT instead of a full dose provocation in search of a save alternative. All controls had a negative oral graded DPT with moxifloxacin (Avelox) up to a cumulative dose of 750 mg. Statistical analysis was performed with IBM SPSS Statistics 22 (IBM Corp, Armonk, New York). Fisher’s exact tests were used to evaluate significance differences of the skin-test results between patients and controls. SPT and IDT results are displayed in Figure 1. SPT was negative in all patients and controls. Intradermal testing yielded positivity in 10/14 patients. Two patients tested positive at the 1:1000 dilution (0.0016 mg/mL), 2 patients at the 1:100 dilution (0.016 mg/mL), and 6 patients at the 1:10 dilution (0.16 mg/ mL). Of the 14 patients, 4 displayed a negative SPT and IDT. In controls, IDT was also positive in 12 individuals. Of the 16 individuals, 2 tested positive at the 1:100 dilution. Of the 14 individuals who received the 1:10 dilution, 12 tested positive. The remaining 2 manifested a (true) negative result in both SPT and IDT. Sensitivity and specificity of the intradermal testing calculated between patients and controls in this population were 57% and 12.5%, respectively. Positive and negative predictive values were 36% and 25%, respectively. A comparison of IDT between patients and controls yieldedP-values of .192 for the 1:1000 dilution, 1.00 for the 1:100 dilution, and .209 for the 1:10 dilution. This is the first assessment of skin testing for moxifloxacin with a comparative study between patients and controls who tolerated a cumulative dose of 750 mg moxifloxacine during a graded oral DPT. We conclude that SPTs and IDTs with moxifloxacin hydrochloride are unreliable methods to establish a diagnosis of immediate moxifloxacin hypersensitivity. Our data are in line with previous findings that quinolones frequently induce skin-test responses in healthy subjects. It appears that at higher dilutions skin tests remain negative in a majority of patients, whereas higher concentrations are not discriminative between patients and exposed controls. There are studies that show that the time elapsed between the acute reaction and skin tests affects the outcome of the tests, which makes it difficult to interpret. We were unable to assess such an effect because the majority of patients received skin testing within 6 months after the acute reaction, and a longitudinal follow-up study does not seem to be warranted. A limitation of our study is the absence of controlled DPTs as previous research has shown that as few as 1/3 of patients with similar recent convincing reaction histories to quinolones reacted on being challenged with the culprit drug. However, because the time between the reactions and evaluation was relatively short

BASOPHIL ACTIVATION IN THE DIAGNOSIS OF LIFE-THREATENING HYPERSENSITIVITY REACTION TO IODINATED CONTRAST MEDIA: A CASE REPORT

Abstract Hypersensitivity to iodinated radiologic contrast media occurs in 1-3% of patients. A complete allergological work-up requires the identification of the pathogenetic mechanism as well as the identification of safe alternatives. The current diagnostic approach relies upon skin tests, since no other in vitro test is standardized. However skin tests do not have an absolute predictive value, cannot be executed immediately and may expose the patients to the risk of severe reactions. Recently the flow-cytometric evaluation of activated basophils, also known as basophil activation test (BAT) has been introduced. Our case report of a 28-year old female who experienced an anaphylactic shock immediately after administration of iomeprol supports the role of BAT in the diagnosis and management of hypersensitivity reactions to contrast media. The possibility of shortening the diagnostic work-up without endangering the health of patients represents the main advantage of this test.

Influence of IL‐6, IL‐33, and TNF‐α on Human Mast Cell Activation: Lessons from Single Cell Analysis by Flow Cytometry

Mechanisms that govern priming and degranulation of human mast cells (MCs) remain elusive. Besides, most of our knowledge is based on experiments from which data only reflect an average of all stimulated cells. This study aims at investigating the effects of proinflammatory cytokines IL‐6, IL‐33, and TNF‐α on IgE‐dependent and IgE‐independent activation of individual MCs.

Response to Letter Regarding Article, “Allergic Inflammation Is Associated With Coronary Instability and a Worse Clinical Outcome After Acute Myocardial Infarction”

We thank Cervellin et al1 for their interesting comments on our article on allergic inflammation in acute coronary syndromes.2 Kounis et al3 described allergic inflammation to be responsible for acute coronary syndromes, during conditions associated with mast cell activation, including allergic or hypersensitivity and anaphylactic insults. Indeed, eosinophils and mast cells play a key role in the late phase of an allergic response, releasing allergic mediators responsible for coronary vasoconstriction …