Immediate allergic reaction to thiocolchicoside confirmed by skin testing and basophil activation test: A case report and literature review.

BACKGROUND: Thiocolchicoside is a muscle relaxant, anti-inflammatory, and analgesic. Administered orally, intramuscularly, or topically, this drug is used in the symptomatic treatment of muscular spasms and rheumatologic disorders. Despite its extensive use, thiocolchicoside is a very rare sensitizer. OBJECTIVE: To evaluate IgE-mediated reaction to thiocolchicoside by basophil activation test. METHODS: Allergological work-up with skin prick tests, intradermal tests and basophil activation test with thiocolchicoside. RESULTS: We report the first case of immediate reaction to thiocolchicoside confirmed by basophil activation test in addition to positive skin tests. CONCLUSIONS: BAT can be considered a complementary diagnostic tool to demonstrate an IgE-mediated reaction also for muscle relaxant drugs.

Perioperative anaphylaxis to chlorhexidine: Crucial role of in-vitro testing.

BACKGROUND: Chlorhexidine is a synthetic biguanide with a broad antibacterial activity and has become an important cause of perioperative anaphylaxis. OBJECTIVE: Reactions due to chlorhexidine allergy are usually IgE-mediated. The aim of this report is to demonstrate utility of laboratory in-vitro testing for diagnosis. METHODS: We report the case of a 36-year old man who experienced severe anaphylaxis during general anesthesia. He underwent skin tests, specific detection of specific IgE to chlorhexidine and basophil activation test (BAT). RESULTS: Skin tests gave false positive results due to dermographism. So, on the basis of a clinical reaction to chlorhexidine and positive tests for IgE to chlorexidine and BAT, we assessed the diagnosis of chlorhexidine allergy. CONCLUSIONS: Physicians should be aware of the role of chlorhexidine in the etiology of perioperative anaphylaxis. In vitro testing such specific IgE and BAT are useful in patient with suspected chlorexidine allergy and limitation to perform skin tests.

Increased CD95 (Fas) and PD-1 expression in peripheral blood T lymphocytes in COVID-19 patients.

A low count of CD4+ and CD8+ lymphocytes is a hallmark laboratory finding in the coronavirus disease 2019 (COVID-19). Using flow cytometry, we observed significantly higher CD95 (Fas) and PD-1 expression on both CD4+ T and CD8+ T cells in 42 COVID-19 patients when compared to controls. Higher CD95 expression in CD4+ cells correlated with lower CD4+ counts. A higher expression of CD95 in CD4+ and CD8+ lymphocytes correlated with a lower percentage of naive events. Our results might suggest a shift to antigen-activated T cells, expressing molecules increasing their propensity to apoptosis and exhaustion during COVID-19 infection.

Hypersensitivity to major panallergens in a population of 120 patients.

INTRODUCTION: Lipid transfer proteins (LTP), profilin and PR-10 are the most important panallergens in central and southern Italy. Lipid transfer proteins are stable molecules, predominantly present in the fruit peel, which can induce systemic symptoms after ingestion of vegetables. Profilin and PR-10 are randomly distributed in the pulp and peel. Both are labile proteins and usually determine reactions restricted to the oral cavity. Panallergens-specific IgE may cross-react with homologues from different plant sources, due to their conserved structure. AIM: To assess the pattern of sensitization to panallergens and the correlation with the clinical history and the allergological evaluation of food and aeroallergens. MATERIAL AND METHODS: One hundred and twenty patients with adverse reactions after vegetables ingestion underwent skin prick tests (SPT) with commercial extracts of plant-derived foods and inhalant allergens and commercial extracts of LTP, profilin and PR-10. RESULTS: Many patients presented positive SPT with different plant-food allergens. We found that 76 patients were sensitized to LTP, 14 to profilin and 5 to PR-10. In the LTP-sensitized group, 64 (84%) patients suffered from systemic symptoms while the patients sensitized only to profilin referred the oral allergy syndrome. CONCLUSIONS: This study shows a high rate of sensitization to LTP in our population according to the literature about food allergy in our geographical area and confirms the literature data about the symptoms referred by patients with sensitization to panallergens. Panallergens should be considered as clinically relevant food allergens.

A Modified Basophil Activation Test for the Clinical Management of Immediate Hypersensitivity Reactions to Paclitaxel: A Proof-of-Concept Study.

Immediate hypersensitivity reactions (iHSRs) to taxanes are observed in 6% and 4% of gynecologic and breast cancer patients, respectively. Drug desensitization is the only option, as no comparable alternative therapy is available. Surfactants in the taxane formulation have been implicated in the immunopathogenesis of iHSRs, although sporadic skin test (ST) positivity and iHSRs to nab-paclitaxel have suggested the involvement of the taxane moiety and/or IgE-mediated pathomechanisms. In vitro diagnostic tests might offer insights into mechanisms underlying iHSRs to taxanes. The aim of the present study was to address this unmet need by developing a novel basophil activation test (BAT). The study included patients (n = 31) undergoing paclitaxel/carboplatin therapy. Seventeen patients presented with iHSRs to paclitaxel (iHSR-Taxpos), and eleven were tolerant (iHSR-Taxneg). Fourteen patients presented with iHSRs to carboplatin (iHSR-Plpos), and fourteen were tolerant (iHSR-Plneg). The BAT median stimulation index (SI) values were 1.563 (range, 0.02-4.11; n = 11) and -0.28 (range -4.88-0.07, n = 11) in iHSR-Taxpos and iHSR-Taxneg, respectively. The BAT median SI values were 4.45 (range, 0.1-26.7; n = 14) and 0 (range, -0.51-1.65; n = 12) in iHSR-Plpos and iHSR-Plneg, respectively. SI levels were not associated with iHSR severity grading. Comparing BAT results in iHSR-Taxpos and iHSR-Taxneg showed the area under the receiver operator characteristic (ROC) curve to be 0.9752 (p = 0.0002). The cutoff calculated by the maximized likelihood ratio identified 90.91% of iHSR-Taxpos patients and 90.91% of iHSR-Taxneg patients. Comparing BAT results for iHSR-Plpos and iHSR-Plneg showed the area under the ROC curve to be 0.9286 (p = 0.0002). The cutoff calculated by the maximized likelihood ratio identified 78.57% of iHSR-Plpos patients and 91.67% of iHSR-Plneg patients. Most iHSR-Taxpos patients for which ST was available (10/11) scored ST-negative and BAT-positive, whereas most iHSR-Plpos patients for which ST was available (14/14) scored both BAT- and ST-positive. This suggested the intervention of non-IgE-mediated mechanisms in iHSR-Taxpos patients. Consistent with this view, an in silico molecular docking analysis predicted the high affinity of paclitaxel to the degranulation-competent MRGPRX2 receptor. This hypothesis warrants further in vitro investigations. In conclusion, the present study provides preliminary proof-of-concept evidence that this novel BAT has potential utility in understanding mechanisms underlying iHSRs to taxanes.

Influence of Antihistamines on Basophil Activation Test in Food Allergy to Milk and Egg.

BACKGROUND: The basophil activation test (BAT) is used to improve the accuracy of food allergy diagnosis. To date, the influence of antiallergic drugs on BAT reactivity is poorly investigated. The aim of the study was to investigate if BAT results were influenced by antihistamine intake for 3 months in a cohort of patients with IgE-mediated food allergy to milk or egg. METHODS: A retrospective, single-center, observational study was performed. We enrolled subjects with history of hypersensitivity reaction after specific food ingestion, positive skin prick tests and specific IgEs, concomitant allergic rhinitis, and, contraindication to the double-blind, placebo-controlled food challenge due to personal history of systemic reactions related to the ingestion of culprit food. Validated allergens (α-lactoalbumin, ß-lactoglobulin, casein, egg white, and yolk) for BAT were used. RESULTS: Thirty-nine patients with well-documented food symptoms and positive allergological workup were included in the study. BAT was positive in 29 patients. The mean percentages of CD63+ expression to specific culprit allergen did not change after the administration of drugs. CONCLUSIONS: This was the first study assessing the effects of oral antihistamines on basophil reactivity in cow's milk and egg food allergy. Antihistamines do not interfere with BAT results.

Utility of Basophil Activation Test for monitoring the acquisition of clinical tolerance after oral desensitization to cow's milk: Pilot study.

OBJECTIVE: The quantification of basophil activation by flow cytometry is a useful tool for the assessment of immediate-type responses to food allergens and the prediction of clinical tolerance in food allergy patients. The aim of this study is to investigate how the analysis of allergen-induced CD63 up-regulation by flow cytometry can be effective in monitoring the acquisition of clinical tolerance by specific oral desensitization in food allergy. To our knowledge, this is the first study to examine this topic. MATERIALS AND METHODS: Three male patients affected by cow's milk allergy underwent successful oral desensitization to cow's milk. In order to monitor the acquired clinical tolerance that occurred after treatment, we performed laboratory tests for total and specific IgE, specific IgG4 and the Basophil Activation Test (BAT) both at baseline and at the end of the desensitization protocol. RESULTS: Using a fluorescent enzyme immunoassay, the comparison of specific cow's milk antibodies before and after treatment showed a decrease of specific IgE levels, without reaching normal values, and an increase of specific IgG4 levels. A complete suppression of cow's milk proteins (α-lactoalbumin, ß-lactoglobulin and casein) induced CD63 regulation was observed in all three reported cases. CONCLUSIONS: Using flow cytometry, food allergen-specific basophil responses could be monitored in order to identify an acquired tolerance induced by desensitization treatment. Although further studies are needed to develop this important new topic, it was interesting to note that the BAT seemed to be more sensitive and characterized by a close correlation with clinical tolerance.