UNASSIGNED: Management of severe allergic transfusion reactions (ATR) is challenging. In this study, we investigate the usefulness of skin tests and basophil activation tests (BAT) in chronically transfused patients for the prevention of future ATR.
UNASSIGNED: BAT and skin tests were carried with the supernatant of red blood cell (RBC) units for a sickle-cell disease patient under chronic exchange transfusion who has presented a severe ATR, in order to prevent potential future ATR. If the results for both BAT and skin tests were negative, the RBC units could be transfused to the patient. If either one of the results was positive, the tested RBC unit was discarded for the patient.
UNASSIGNED: 192 RBC units were tested with both tests. The level of results concordance between the two tests was 95%. Out of the 169 negative units with both tests, 118 units were transfused to the patient for which he presented no ATR.
UNASSIGNED: In our study, combining both BAT and skin tests was associated with a good negative predictive value since we were able to safely transfuse our patient. Further studies are still necessary to confirm this result but this pilot study indicates that skin tests and BAT might help prevent ATR. When BAT is not available, skin tests may also be useful in preventing ATR.

The gold standard for diagnosing egg allergy in children is the oral food challenge (OFC). However, OFCs are time-consuming and risky procedures. Our study aimed to evaluate the utility of the basophil activation test (BAT) and component-resolved diagnostic in the diagnostic workup of children with egg allergy.
Overall, 86 children aged 6 months to 17 years, suspected of egg allergy, underwent OFC with boiled egg according to international standardized protocols. BAT and specific immunoglobulin E (sIgE) testing to component egg proteins (Gal d 1-4) were also performed.
Of the 22 children who reacted to boiled egg, only one experienced anaphylaxis during the challenge. BAT was performed in samples obtained by 75 of the 86 patients of our cohort. Egg white and yolk protein extracts induced CD63 upregulation in the egg-allergic (EA) children compared with sensitized children that tolerated boiled egg (we registered an overall mean of CD63 expression in the EA population of 44.4% [SD 34.1] for egg white and 34.7% [SD 31.3] for egg yolk vs. 12.5% [SD 19.1] and 10.0% [SD 16.0] in sensitized children). BAT could discriminate between true egg allergy and egg sensitization in our population. As a second-line diagnostic step, the positivity of BAT for egg white or Gal d 1-sIgE resulted in a 40.9% OFC reduction, especially for those with a positive outcome.
The BAT may be implemented in the diagnostic workup of egg allergy in children and, in a stepwise approach, separately or combined with Gal d 1-sIgE, may predict the allergic status and reduce the number of positive OFCs in children with egg allergy at low risk for severe reactions.

The rising popularity of undercooked or raw seafood containing larvae of the Anisakis parasite has led to issues of public health concern due to allergic manifestations. We conducted an observational study on the use of an innovative Anisakis allergy diagnostic algorithm in a convenience sample of 53 allergic outpatients recruited in Western Sicily, between April 2021 and March 2022. We included individuals with an anamnesis suggestive of IgE sensitization to Anisakis reporting clinical manifestation in the last month due to allergic reactions after eating fresh fish, or in subjects at high exposure risk with sea products while abstaining from fish ingestion, excluding those with documented fish sensitization. Outpatients were tested via Skin Prick Test, IgE-specific dosage and Basophil Activation Test (BAT). Twenty-six outpatients were diagnosed with Anisakis, while 27 with Chronic Urticaria (CU). We found a seven-fold excess risk for Anisakis (p4) positivity in the Anisakis allergic outpatients, as compared to the CU ones. BAT showed the best diagnostic accuracy (92.45%) and specificity (100%), while specific IgE to Ascaris (p1) documented the best sensitivity (92.31%) but a very low specificity (37.04%). In conclusion, our findings may represent a potentially useful contribution to the future development of updated clinical guidelines.

Diagnosis of perioperative anaphylaxis is often challenging. This study describes the utility of a newly developed tool for identifying patients with a high possibility of anaphylaxis, and aimed to investigate the frequency of anaphylaxis with each drug during the perioperative period in Japan.
This study included patients with anaphylaxis of Grade 2 or higher severity during general anaesthesia at 42 facilities across Japan in 2019 and 2020. We developed and adopted a unique objective evaluation tool yielding a composite score for diagnosing anaphylaxis, which includes the results of skin tests and basophil activation tests, and clinical scores for perioperative anaphylaxis. The number of cases using each drug and the total number of anaphylaxis cases were investigated to calculate the frequency of anaphylaxis.
General anaesthesia was performed in 218 936 cases, which included 55 patients with suspected perioperative anaphylaxis. The developed composite score diagnosed 43 of them with a high probability of anaphylaxis. The causative agent was identified in 32 cases. Plasma histamine levels showed high diagnostic accuracy for anaphylaxis. The top causative agents were rocuronium (10 cases in 210 852 patients, 0.005%), sugammadex (7 cases in 150 629 patients, 0.005%), and cefazolin (7 cases in 106 005 patients, 0.007%).
We developed a composite tool to diagnose anaphylaxis, and found that the combination of tryptase levels, skin testing, and basophil activation testing results and clinical score improved the certainty of anaphylaxis diagnosis. The incidence of perioperative anaphylaxis in our study was 1 in about 5000 general anaesthesia cases.
UMIN000035350.

Studies on the efficacy of peanut sublingual immunotherapy (SLIT) are limited. The durability of desensitization after SLIT has not been well described.
We sought to evaluate the efficacy and safety of 4-mg peanut SLIT and persistence of desensitization after SLIT discontinuation.
Challenge-proven peanut-allergic 1- to 11-year-old children were treated with open-label 4-mg peanut SLIT for 48 months. Desensitization after peanut SLIT was assessed by a 5000-mg double-blind, placebo-controlled food challenge (DBPCFC). A novel randomly assigned avoidance period of 1 to 17 weeks was followed by the DBPCFC. Skin prick test results immunoglobulin levels, basophil activation test results, TH1, TH2, and IL-10 cytokines were measured longitudinally. Safety was assessed through patient-reported home diaries.
Fifty-four participants were enrolled and 47 (87%) completed peanut SLIT and the 48-month DBPCFC per protocol. The mean successfully consumed dose (SCD) during the DBPCFC increased from 48 to 2723 mg of peanut protein after SLIT (P < .0001), with 70% achieving clinically significant desensitization (SCD > 800 mg) and 36% achieving full desensitization (SCD = 5000 mg). Modeled median time to loss of clinically significant desensitization was 22 weeks. Peanut skin prick test; peanut-specific IgE, IgG4, and IgG4/IgE ratio; and peanut-stimulated basophil activation test, IL-4, IL-5, IL-13, IFN-γ, and IL-10 changed significantly compared with baseline, with changes seen as early as 6 months. Median rate of reaction per dose was 0.5%, with transient oropharyngeal itching being the most common, and there were no dosing symptoms requiring epinephrine.
In this open-label, prospective study, peanut SLIT was safe and induced clinically significant desensitization in most of the children, lasting more than 17 weeks after discontinuation of therapy.

BACKGROUND: One of the main barriers to vaccination against SARS-CoV-2 is the fear of developing hypersensitivity reactions to any of its components. Although these reactions are very rare, it is necessary to establish an effective protocol to detect patients at risk of developing them. The aim of this study was to evaluate hypersensitivity reactions in vaccinated patients in order to allow or not to complete the vaccination protocol.
METHODS: Descriptive and cross-sectional study in which patients with suspected hypersensitivity to SARS-CoV-2 vaccines were evaluated. All patients underwent skin prick test (SPT) and/or intradermal test (IDT) with the vaccines and their excipients. In patients with positive IDT with the vaccine, a histopathological and immunohistochemical study was performed by skin biopsy. A basophil activation test (BAT) and a lymphoblastic transformation test (LTT) were also performed.
RESULTS: Sixteen patients with suspected hypersensitivity to SARS-CoV-2 vaccine (12 received Comirnaty®, 3 received Vaxzevria®, and 1 received Spikevax®) were evaluated. Half had immediate hypersensitivity reactions and half had delayed reactions. All SPTs to excipients and vaccines were negative. IDTs with all excipients were negative. IDTs with vaccines were positive in 11 patients and negative in 5. The histological and immunohistochemical study of the two selected patients with positive IDT with vaccine showed T-lymphocyte involvement. BAT and LTT were negative in both cases. The vaccination protocol could be completed in 7 of 16 patients (44%) studied. The remaining 9 patients did not receive the second dose: 5 because vaccination was not required and 4 because they refused to be vaccinated.
CONCLUSIONS: Thanks to the allergological and immunohistochemical study, the vaccination protocol could be completed in about half of the patients who presented suspected hypersensitivity reactions to SARS-CoV-2 vaccines. IDTs with vaccines could be a valuable method for assessing the immunogenicity of the vaccines.

No reliable biological marker for the diagnosis of asthma in younger children is currently available. In this study, we analyzed the differences in basophil activation test (BAT) results among children with recurrent wheezing episodes who had different asthma outcomes.
A prospective cohort study was conducted in children aged under 5 years who visited our pediatric respiratory clinic and ward for wheezing. After enrollment, the participants provided samples for a CD63-based BAT performed using an inhalant allergen mixture as a stimulant. Histories of personal allergic diseases and family allergic diseases were evaluated by using a questionnaire. All participants were followed up for 2 years, and their asthma outcomes were evaluated at the end of the follow-up period. The correlation between the BAT results and asthma outcomes was analyzed. Of the 45 originally enrolled children, 38 completed both the follow-up and a BAT. After stimulation with the inhalant mixture, the CD63 expression on basophils and the rate of positive CD63-based BAT results in children diagnosed with asthma were both significantly higher than those in children who were not diagnosed with asthma (p < 0.05 and p < 0.01, respectively). For the prediction of asthma, the positive predictive value and negative predictive value of CD63-based BAT was 71.8 and 69.2%, respectively. The positive likelihood ratio and negative likelihood ratio of CD63-based BAT were 1.70 and 0.3, respectively.
Our pilot study indicates that CD63-based BAT has potential clinical value for predicting asthma outcome in young children with wheezing episodes.

Background: Allergic bronchopulmonary mycosis (ABPM) is an underestimated allergic disease due to fungi. Most reported cases are caused by Aspergillus fumigatus (Af) and are referred to as allergic bronchopulmonary aspergillosis (ABPA). The main risk factor of ABPA is a history of lung disease, such as cystic fibrosis, asthma, or chronic obstructive pulmonary disease. The main diagnostic criteria for ABPA rely on the evaluation of humoral IgE and IgG responses to Af extracts, although these cannot discriminate Af sensitization and ABPA. Moreover, fungi other than Af have been incriminated. Flow cytometric evaluation of functional responses of basophils and lymphocytes in the context of allergic diseases is gaining momentum. Objectives: We hypothesized that the detection of functional responses through basophil and lymphocyte activation tests might be useful for ABPM diagnosis. We present here the results of a pilot study comparing the performance of these cellular assays vs. usual diagnostic criteria in a cystic fibrosis (CF) cohort. Methods: Ex vivo basophil activation test (BAT) is a diagnostic tool highlighting an immediate hypersensitivity mechanism against an allergen, e.g., through CD63 upregulation as an indirect measure of degranulation. Lymphocyte stimulation test (LST) relies on the upregulation of activation markers, such as CD69, after incubation with allergen(s), to explain delayed hypersensitivity. These assays were performed with Af, Penicillium, and Alternaria extracts in 29 adult CF patients. Results: BAT responses of ABPA patients were higher than those of sensitized or control CF patients. The highest LST result was for a woman who developed ABPA 3 months after the tests, despite the absence of specific IgG and IgE to Af at the time of the initial investigation. Conclusion: We conclude that basophil and lymphocyte activation tests could enhance the diagnosis of allergic mycosis, compared to usual humoral markers. Further studies with larger cohorts and addressing both mold extracts and mold relevant molecules are needed in order to confirm and extend the application of this personalized medicine approach.

Although cases of anaphylaxis caused by sugammadex have been reported, its incidence remains uncertain. Conversely, no studies have evaluated the incidence of anaphylaxis to neostigmine.
This was a retrospective multicentre observational study of patients who underwent surgery under general anaesthesia between 2012 and 2016 to compare the incidence of anaphylaxis with sugammadex with that of neostigmine at four tertiary hospitals in Japan. To ensure the quality of diagnosis, only cases with a clinical history suggestive of anaphylaxis, along with positive results from in vitro or in vivo testing, were assessed.
From a total of 49 532 patients who received general anaesthesia included in this study, 18 cases of anaphylaxis were reported, of which six were attributable to sugammadex and none to neostigmine. There were no fatalities attributable to anaphylaxis. The incidence of anaphylaxis caused by all drugs or by sugammadex was calculated as 0.036% (95% confidence interval [CI]: 0.022-0.057%) and 0.02% (of the number of sugammadex cases) (95% CI: 0.007-0.044%), respectively.
The results suggest that neostigmine might be safer than sugammadex when assessing only the incidence of anaphylaxis. We believe that there is room for reconsideration of the choice of reversal agent for neuromuscular blocking agents by all anaesthetists.
UMIN000022365; UMIN000033561.

BACKGROUND: Data on local intraoperative anaphylaxis in Hong Kong is scarce, with few reviews available. We aimed to study the characteristics, presentations and workup results of cases referred to a local allergy clinic.
METHODS: A retrospective review was performed of patient referrals and workup results for suspected intraoperative anaphylaxis at Queen Mary Hospital drug allergy clinic in 2012-2016.
RESULTS: Tryptase was checked in only 81.7% (49/60) of the cases, most of which showed elevation (71.4%, 35/49). Among the 59 patients who received a workup, 47 (79.7%) showed positive findings, with a particularly high yield in the tryptase-positive subgroup (88.6%, 31/35). Among the 54 patients who consented to skin tests (the most sensitive investigation), 43 (79.6%) cases were positive. Overall, neuromuscular blockers were the commonest cause (25.0%, 15/60) of intraoperative anaphylaxis, while antibiotics ranked second (23.3%, 14/60). The timing of reactions was an important indication of potential allergens. For example, the majority of the neuromuscular blocker allergies occurred during the induction phase, while all gelofusine allergic events were in the maintenance phase of anaesthesia. 13 (21.7%) out of 60 cases received subsequent general anaesthesia procedures, with no recurrence of allergic reactions.
CONCLUSIONS: Proper workup after an intraoperative anaphylactic event has a fairly good chance of identifying the causative allergen. These results are useful for patient management and the planning of subsequent anaesthetic procedures.