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Sugammadex hypersensitivity is an emerging safety concern. We aimed to describe the clinical and diagnostic features of perioperative hypersensitivity to sugammadex, and secondarily to provide an estimate of perioperative sugammadex hypersensitivity incidence in Australia. We retrospectively analysed cases of hypersensitivity to sugammadex diagnosed by positive intradermal or skin prick testing at six perioperative allergy clinics in Australia. We included all grades of hypersensitivity and compared life-threatening with non-life-threatening presentations. Incidence of hypersensitivity events was estimated relative to the estimated number of sugammadex administrations across two health services between January 1, 2010 and June 30, 2023. Thirty cases were included (15 life-threatening and 15 non-life-threatening). The most common clinical signs were hypotension (n =25, 83.3%) and flushing/erythema (n =21, 70%). The median time to recognition of hypersensitivity was 5 (interquartile range 2–7.5) min. Five cases were recognised 10–30 min after administration. Serum tryptase was measured in 28 (93.3%) patients. Tryptase was positive in 15 (100%) life-threatening cases and nine (69.2%) non-life-threatening cases. The estimated incidence of sugammadex hypersensitivity was 0.004% (95% confidence interval 0.002–0.008%). Sugammadex hypersensitivity presents similarly to other causes of perioperative hypersensitivity, however recognition can be delayed. The combination of positive serum tryptase and positive skin tests suggests an IgE-mediated mechanism of hypersensitivity. The estimated incidence of sugammadex hypersensitivity in Australia is lower than earlier reports. [ABSTRACT FROM AUTHOR]

Most post-mortem examinations in the United Kingdom (UK) are currently performed at the request of the Coroner to differentiate between natural and unnatural causes of death on balance of probabilities. This has curtailed the remit of the practicing pathologist to only include additional investigations where the results of which would directly influence the cause of death given. The current review discusses sudden unexpected causes of death where additional investigations are required to make the correct diagnosis in certain circumstances. It is focused at pathologists working within Coronial systems and on causes of death outside the cardiovascular and central nervous systems. Specifically, we discuss the utility of cultures in sepsis, histology in unexpected tumours and special investigations in pneumothorax, asthma, anaphylaxis, diabetes mellitus, insulin-overdose, acute pancreatitis, acute liver failure and acute kidney injury. [ABSTRACT FROM AUTHOR]

Conformational epitopes are associated with the development of food allergic tolerance and the severity of food allergy. Peanut can trigger severe anaphylactic reactions, however, the reason behind the severe allergic reactions caused by peanut remains unexplained. The purpose of this article was to provide an explanation for the severe allergy caused by peanut, focusing on the conformational epitopes of Ara h 5 and Ara h 8 allergens that exhibit cross-reactivity with asthma reactions. Ara h 5 and Ara h 8 proteins were prepared by an Escherichia coli expression system. IgE reactivity of 37 patients with allergy toward Ara h 5 and Ara h 8 allergens was assessed by using IgE-binding assays, dot blot and western blot. The allergenicity of Ara h 5 and Ara h 8 protein was analysed in mouse model. Conformational IgE epitopes of Ara h 5 was identified using phage peptide library and the Pepitope Server. Compared to Ara h 8, the conformational epitope of Ara h 5 protein was crucial in the process of sensitization. Ara h 5 showed a stronger IgE reactivity and the ability to induce β-hexosaminidase release. Ara h 5 caused more severe lung inflammation than Ara h 8 protein. While Ara h 8 caused more severe intestinal inflammation than Ara h 5. The results showed that the conformational epitope sequences of Ara h 5 were WETIYSR and FHWWYLK. The results provide a theoretical basis for the production of hypoallergenic peanut protein and the immunotherapy of peanut allergy. • The conformational epitope of Ara h 5 protein was crucial in the process of sensitization. • Ara h 5 allergen induced more severe inflammation than Ara h 8 in mice. • The conformational epitopes WETIYSR and FHWWYLK for murine antibody were identified in the Ara h 5. [ABSTRACT FROM AUTHOR]

This quality improvement project uses high-fidelity simulation to evaluate a registered nurse (RN)–initiated protocol to treat anaphylactoid contrast reactions, with a secondary outcome to measure the effects of simulation on RN confidence. Anaphylactoid reactions are rare life-threatening occurrences in radiology departments. Recently updated professional recommendations allow the expansion of the RN role in supervising and treating contrast reactions. Forty-six radiology nurses and 5 providers participated in simulated contrast reactions. Time to recognition and treatment were recorded. Simulation was assessed via a validated tool, and RN confidence was measured with presurveys and postsurveys. Feasibility of a symptom-driven assessment tool and RN protocol to manage contrast reaction until physician arrival were evaluated. Time from recognition of reaction to treatment was significantly longer using an RN protocol (difference = 102, 95% confidence interval: (64, 140), p value <.001), although not clinically significant. Presurvey and postsurveys demonstrated increased RN confidence in 10 measures, and a validated tool found 85% of responses to simulation favorable. Treating contrast reactions via RN protocol may be clinically useful for managing severe contrast reactions when a physician is not immediately available. Simulation significantly increases RN confidence and should be considered for continuing education. • Contrast media reactions are rare, potentially life-threatening occurrences. • Changes in regulatory guidance enable nurses to supervise contrast administration. • Nursing scope of practice requires orders to administer medication for reactions. • Nurse-initiated protocols can generate orders for rapid epinephrine administration. • High-fidelity simulation improves nurse confidence treating anaphylactic reactions. [ABSTRACT FROM AUTHOR]

To retrospectively assess the incidence and severity of perioperative protamine reactions in adult patients with documented history of fish allergy. Retrospective observational study. Large academic tertiary referral center. Adults with fish allergies undergoing surgeries involving protamine, between January 1, 2008, and March 1, 2018. Perioperative protamine administration in patients with documented fish allergy. Perioperative protamine and anaphylactic reactions were reviewed. A diagnosis of anaphylaxis or protamine reaction was based on clinical suspicion, perioperative events, and postoperative evaluations. Among 214 patients, 2 cases (<1%) of anaphylaxis or protamine reactions occurred. Cardiac procedures were most common (67%). The median intraoperative heparin dosage was 46,000 IU, and the median protamine dosage was 310 mg. Nearly all patients (99%) were admitted to the intensive care unit postoperatively, with a median hospital stay of 6.5 days (interquartile range, 5.2-14.6 days). There were 3 deaths (1%) within 30 days, and 15 (7%) within 1 year. The study findings suggest that in patients with a history of fish allergy, cross-reactivity with protamine is unlikely, as anaphylaxis and/or protamine reactions were rare in this patient population in the perioperative environment. Based on these findings, this study does not recommend avoiding protamine solely based on a history of fish allergy when heparin reversal is required during surgery. [ABSTRACT FROM AUTHOR]

Polyethylene glycol (PEG) is sometimes included in temporary endodontic filling materials to modify viscosity. PEG is considered a low hazard chemical, but parenteral PEG exposure is associated with a risk of anaphylaxis. We report 2 cases of anaphylaxis after treatment with an endodontic temporary filling material containing PEG. One patient survived after hospital treatment, but the second case was fatal. Extensive investigations were needed to find the culprit. Allergic reactions to PEG are increasingly reported and have significant implications for the patient. Precautionary measures are discussed. [ABSTRACT FROM AUTHOR]

Aquagenic urticaria is a very rare form of physical urticaria with less than 50 cases reported in the medical literature. The condition causes itchy and potentially painful hives to break out whenever the sufferer comes into contact with water, sweat, or tears. A relationship between chronic urticaria and systemic lupus erythematosus (SLE) has been suggested in the literature. However, aquagenic urticaria has rarely been reported in association with other systemic conditions and is not typically a life-threatening condition. There are no documented cases of aquagenic urticaria occurring together with SLE or small vessel vasculitis, or presenting with cutaneous lesions more serious than urticaric wheals. This report presents a rare case of a 43-year-old African-American woman with aquagenic urticaria, who developed unusually painful skin ulcerations and life-threatening wheezing after contact with water, remained misdiagnosed for over five years, and, subsequently developed several serious comorbidities, including SLE. The case seems to suggest that aquagenic urticaria, urticarial vasculitis, and SLE may be related disorders that potentially developed along one spectrum of disease. As diagnosis of the condition is challenging and the use of water intraorally is essential to performing most dental procedures, the article aims to raise awareness of the condition among dentists and physicians and provides tips and suggestions to help manage patients with aquagenic urticaria more effectively. [ABSTRACT FROM AUTHOR]

• The largest series of pediatric cases of immediate hypersensitivity related to chlorhexidine, mostly represented by anaphylaxis (grades II–IV), confirmed by allergy tests and diagnosed in France. • In the setting of domestic use and misuse of chlorhexidine at home. • Hypothesis of sensitization, increases in case numbers, context of recurrence, and measures to prevent immediate allergies to chlorhexidine. Immediate allergic reactions to chlorhexidine have been clearly identified in numerous countries, generating governmental warnings worldwide. The aim of our study was to characterize (i) these allergies, which are less reported in pediatric populations, and (ii) the patient-at-risk profile so as to suggest preventive measures. In association with the allergy department and the regional pharmacovigilance center in Rennes University Hospital, France, a multicenter retrospective, descriptive, and observational study was conducted using data from the national pharmacovigilance database for the period of January 1, 2010 to June 30, 2020. Immediate allergies to chlorhexidine cases based on a clinical history compatible with an immunoglobulin E (IgE)-mediated reaction, along with positive allergic testing, were analyzed. Of the 478 cases identified, 17 pediatric cases of immediate allergic reaction to chlorhexidine (13 cases of grades II–IV anaphylaxis) were retained for the analysis. For 58.8 % of these cases, a history of a previous more moderate reaction to the substance was identified. The reactions occurred most frequently in cases of domestic misuse (88.2 %, n = 15/17) of chlorhexidine to dress a wound. Recurrence was reported for two cases, later leading to severe reactions at each new exposure to the allergen, suggesting an aggravation mechanism. The number of pediatric cases of immediate allergies to chlorhexidine has possibly been underestimated on account of insufficient knowledge of the allergy and in view of its common usage. Information on the method of caring for wounds among children and on the risk of allergic sensitization as well as exploring any unusual reaction to chlorhexidine application could reduce the number of allergic reactions. [ABSTRACT FROM AUTHOR]

Histamine is one of the most important and extensively studied biological molecules in the human body. It plays a constitutive role within almost every bodily system, but most notably within the stomach, where it regulates acid secretion, the central nervous system, where it acts as a neurotransmitter, the cardiovascular system, where it affects cardiac output and vascular permeability, and it has a well-established role in allergy and anaphylaxis. Histamine exerts its effects through four distinct receptor subtypes: H1, H2, H3 and H4. Predominantly, though not exclusively, these take the form of G-protein-coupled receptors. Clinically used antihistamines demonstrate inverse agonism to the histamine receptor and drugs are available with activity at H1, H2 and H3 receptors. H1 antihistamines are used in the treatment of allergy, and are classified as either first or second generation. First-generation antihistamines have significant sedative side effects. H2 antihistamines are predominantly used for the treatment of gastrooesophageal reflux and peptic ulcer disease; however, the most widely used of these, ranitidine, has been withdrawn from use due to (impurity related) safety concerns. H3 antihistamines have been explored for the treatment of neurological disease and to date the only licensed H3 antihistamine is used for the treatment of narcolepsy. Multiple uses have been suggested for H4 antihistamines, including immunomodulation, the treatment of asthma and even as an analgesic. However, no (commercially available) drug exists as of yet. [ABSTRACT FROM AUTHOR]

[Display omitted] Oral consumption of peanut products early in life reduces the incidence of peanut allergy in children. However, little is known about whether exposure via the oral mucosa alone is sufficient or whether the gastrointestinal tract must be engaged to protect against peanut allergy. We used a mouse model and examined the effects of peanut allergen administration to only the oral cavity on allergy development induced by environmental exposure. Naive BALB/c mice were administered peanut flour (PNF) sublingually, followed by epicutaneous exposure to PNF to mimic a human condition. The sublingual volume was adjusted to engage only the oral cavity and prevent it from reaching the esophagus or gastrointestinal tract. The efficacy was evaluated by examining the anaphylactic response, antibody titers, and T follicular helper cells. The mice exposed epicutaneously to PNF developed peanut allergy, as demonstrated by increased plasma levels of peanut-specific IgE and the manifestation of acute systemic anaphylaxis following intraperitoneal challenge with peanut extract. The development of peanut allergy was suppressed when mice had been given PNF sublingually before epicutaneous exposure. There were fewer T follicular helper cells in the skin-draining lymph nodes of mice that received sublingual PNF than in the mice that received PBS. Suppression of IgE production was observed with sublingual PNF at 1/10 of the intragastric PNF dose. Administration of peanut allergens only to the oral cavity effectively prevents the development of peanut allergy. The capacity of the oral mucosa to promote immunologic tolerance needs to be evaluated further to prevent food allergy. [ABSTRACT FROM AUTHOR]

Perioperative anaphylaxis is a serious and often life-threatening immediate hypersensitivity reaction. There are few published data on paediatric perioperative anaphylaxis (pPOA). We evaluated the incidence of and risk factors involved in the occurrence of pPOA within a large US national database. Deidentified data from the US Nationwide Inpatient Sample from 2005 to 2014 were used to identify pPOA cases and to conduct a retrospective multivariate analysis of preselected independent variables. Among 3,601,180 surgeries and procedures in children aged 0–18 yr, 297 pPOA cases were identified for an incidence of one in 12,125 surgeries and procedures. Compared with controls, pPOA cases had an increased median length of stay (6 vs 2 days; P <0.001) and median hospital cost ($54 719 vs $5109; P <0.0001). The age groups between 6 and 12 yr (odds ratio [OR] 7.1; 95% confidence interval [CI] 3.9–12.9; P <0.001) and 13 and 17 yr (OR 8.5; 95% CI 4.7–15.2; P <0.001) were associated with increased odds of pPOA. Transplant (OR 46.3; 95% CI 20.8–102.9; P <0.001), cardiac (OR 16.4; 95% CI 7.5–35.9; P <0.001), and vascular (OR 15.2; 95% CI 7.5–30.7; P <0.001) procedures posed the highest risk for pPOA. Chronic pulmonary disease, coagulopathy, and fluid and electrolyte disorders were also associated with pPOA (OR 2.2; 95% CI 1.5–3.3; P <0.001). The incidence of pPOA was one in 12,125 cases. Risk factors included age, procedure type, and comorbidities. [ABSTRACT FROM AUTHOR]

Mast cell–derived mediators induce vasodilatation and fluid extravasation, leading to cardiovascular failure in severe anaphylaxis. We previously revealed a synergistic interaction between the cytokine IL-4 and the mast cell–derived mediator histamine in modulating vascular endothelial (VE) dysfunction and severe anaphylaxis. The mechanism by which IL-4 exacerbates histamine-induced VE dysfunction and severe anaphylaxis is unknown. We sought to identify the IL-4–induced molecular processes regulating the amplification of histamine-induced VE barrier dysfunction and the severity of IgE-mediated anaphylactic reactions. RNA sequencing, Western blot, Ca2+ imaging, and barrier functional analyses were performed on the VE cell line (EA.hy926). Pharmacologic degraders (selective proteolysis-targeting chimera) and genetic (lentiviral short hairpin RNA) inhibitors were used to determine the roles of signal transducer and activator of transcription 3 (STAT3) and STAT6 in conjunction with in vivo model systems of histamine-induced hypovolemic shock. IL-4 enhancement of histamine-induced VE barrier dysfunction was associated with increased VE-cadherin degradation, intracellular calcium flux, and phosphorylated Src levels and required transcription and de novo protein synthesis. RNA sequencing analyses of IL-4–stimulated VE cells identified dysregulation of genes involved in cell proliferation, cell development, and cell growth, and transcription factor motif analyses revealed a significant enrichment of differential expressed genes with putative STAT3 and STAT6 motif. IL-4 stimulation in EA.hy926 cells induced both serine residue 727 and tyrosine residue 705 phosphorylation of STAT3. Genetic and pharmacologic ablation of VE STAT3 activity revealed a role for STAT3 in basal VE barrier function; however, IL-4 enhancement and histamine-induced VE barrier dysfunction was predominantly STAT3 independent. In contrast, IL-4 enhancement and histamine-induced VE barrier dysfunction was STAT6 dependent. Consistent with this finding, pharmacologic knockdown of STAT6 abrogated IL-4–mediated amplification of histamine-induced hypovolemia. These studies unveil a novel role of the IL-4/STAT6 signaling axis in the priming of VE cells predisposing to exacerbation of histamine-induced anaphylaxis. [ABSTRACT FROM AUTHOR]

[Display omitted] Growing evidence demonstrates the importance of high- and low-density lipoprotein cholesterol in certain immune and allergy-mediated diseases. This study aimed to evaluate levels of high- and low-density lipoprotein cholesterol and apolipoproteins A1 and B in sera from a cohort of patients presenting with hypersensitivity reactions. We further assessed the function of high-density lipoprotein particles as well as their involvement in the molecular mechanisms of anaphylaxis. Lipid profile determination was performed in paired (acute and baseline) serum samples from 153 patients. Thirty-eight experienced a non-anaphylactic reaction and 115 had an anaphylactic reaction (88 moderate and 27 severe). Lecithin cholesterol acyl transferase activity was assessed in patient sera, and we also evaluated macrophage cholesterol efflux in response to the serum samples. Last, the effect of anaphylactic-derived high-density lipoprotein (HDL) particles on the endothelial barrier was studied. Detailed methods are provided in the Methods section in this article's Online Repository available at www.jacionline.org. Serum samples from severe anaphylactic reactions show statistically significant low levels of HDL cholesterol, low-density lipoprotein cholesterol, and apolipoproteins A1 and B, which points to their possible role as biomarkers. Specifically, HDL particles play a protective role in cardiovascular diseases. Using functional human serum cell assays, we observed impaired capacity of apolipoprotein B–depleted serum to induce macrophage cholesterol efflux in severe anaphylactic reactions. In addition, purified HDL particles from human anaphylactic sera failed to stabilize and maintain the endothelial barrier. These results encourage further research on HDL functions in severe anaphylaxis, which may lead to new diagnostic and therapeutic strategies. [ABSTRACT FROM AUTHOR]

IgE-mediated degranulation of mast cells (MCs) provides rapid protection against environmental hazards, including animal venoms. A fraction of tissue-resident MCs intimately associates with blood vessels. These perivascular MCs were reported to extend projections into the vessel lumen and to be the first MCs to acquire intravenously injected IgE, suggesting that IgE loading of MCs depends on their vascular association. We sought to elucidate the molecular basis of the MC–blood vessel interaction and to determine its relevance for IgE-mediated immune responses. We selectively inactivated the Itgb1 gene, encoding the β1 chain of integrin adhesion molecules (ITGB1), in MCs by conditional gene targeting in mice. We analyzed skin MCs for blood vessel association, surface IgE density, and capability to bind circulating antibody specific for MC surface molecules, as well as in vivo responses to antigen administered via different routes. Lack of ITGB1 expression severely compromised MC–blood vessel association. ITGB1-deficient MCs showed normal densities of surface IgE but reduced binding of intravenously injected antibodies. While their capacity to degranulate in response to IgE ligation in vivo was unimpaired, anaphylactic responses to antigen circulating in the vasculature were largely abolished. ITGB1-mediated association of MCs with blood vessels is key for MC immune surveillance of blood vessel content, but is dispensable for slow steady-state loading of endogenous IgE onto tissue-resident MCs. [ABSTRACT FROM AUTHOR]

Les allergies alimentaires touchent environ 6 à 8 % des enfants. Les légumineuses sont les ingrédients les plus communs dans le régime méditerranéen. Elles occupent la cinquième place parmi les aliments responsables de réaction allergique qui peuvent être sévères et provoquer des anaphylaxies. Les lentilles sont le plus impliquées dans les allergies alimentaires IgE médiée chez les enfants. Cependant, peu d'informations sont disponibles sur les allergènes de lentilles. Le but de cette étude est de décrire le tableau clinique et biologique de l'allergie alimentaire aux lentilles dans le but de sensibiliser les pédiatres à cet allergène émergent. Nous rapportons 4 cas d'allergie alimentaire aux lentilles chez des enfants âgés de 3 à 6 ans dont 2 de sexe masculin. Les symptômes cliniques sont survenus dans les deux heures suivant l'ingestion ou à l'inhalation de vapeur de lentilles. Trois patients ont consulté pour des réactions urticariennes localisées ou généralisées dont un avec un angioœdème du visage. Un patient avait consulté à plusieurs reprises pour des malaises inexpliqués après les repas. Un terrain d'atopie personnelle ou familiale a été retrouvé chez 3 malades. Parmi ces patients deux avaient d'autres allergies alimentaires associées : au poisson (2 cas), à l'arachide (1 cas), à l'œuf (2 cas) et aux crevettes (1 cas). Un retard pondéral a été objectivé chez un de nos malades (–2 DS). Les Prick-tests à l'allergène natif se sont révélés très positifs chez deux enfants et ont permis de confirmer le diagnostic. Ils étaient douteux dans un cas et n'ont pas été faits chez un enfant au tableau clinique très sévère. Le dosage des IgE spécifiques est revenu très positif une fois. L'évolution était favorable dans tous les cas. La prise en charge a consisté en une éviction stricte des lentilles crues ou cuites ainsi que des autres aliments dans le cadre d'allergie alimentaire croisée. L'allergie aux lentilles est rare dans notre contexte. Son diagnostic repose sur une anamnèse évocatrice, suivie en cas de doute par un test de provocation orale. Elle est due essentiellement à l'allergène majeur viciline Len c 1. Elle peut être associée une hypersensibilité à d'autres légumineuses appartenant à la même famille notamment les petits pois. Son évolution est favorable vers l'acquisition de la tolérance dans la majorité des cas. Food allergies affect about 6–8% of children. Legumes are the most common ingredients in the Mediterranean diet. They occupy the fifth place among the foods responsible for allergic reactions that can be severe and cause anaphylaxis. Lentils are most involved in IgE-mediated food allergies in children. However, little information is available on lentil allergens. The aim of this study is to describe the clinical and biological picture of food allergy to lentils in order to raise awareness of this emerging allergen among pediatricians. We report 4 cases of food allergy to lentils in children aged 3 to 6 years, 2 of whom were male. Clinical symptoms occurred within 2 hours of ingestion or inhalation of lens vapor. Three patients consulted for localized or generalized urticarial reactions, including one with angioedema of the face. One patient had consulted on several occasions for unexplained discomfort after meals. A personal or family atopic background was found in 3 patients. Two of these patients had other associated food allergies: to fish (2 cases), peanut (1 case), egg (2 cases) and shrimp (1 case). One of our patients was found to be underweight (–2 SD). Prick-tests to the native allergen were very positive in two children and confirmed the diagnosis. They were doubtful in one case and were not performed in a child with a very severe clinical picture. The specific IgE assay was very positive in one case. The evolution was favorable in all cases. The management consisted of a strict avoidance of raw or cooked lentils as well as other foods in the context of a cross-food allergy. Allergy to lenses is rare in our context. Its diagnosis is based on a suggestive anamnesis, followed in case of doubt by an oral provocation test. It is essentially due to the major allergen vicilin Len c 1. It may be associated with hypersensitivity to other legumes belonging to the same family, notably peas. In the majority of cases, the disease evolves favorably and tolerance is acquired. [ABSTRACT FROM AUTHOR]

[Display omitted] Human IgE (hIgE) mAbs against major mite allergen Der p 2 developed using human hybridoma technology were used for IgE epitope mapping and analysis of epitopes associated with the hIgE repertoire. We sought to elucidate the new hIgE mAb 4C8 epitope on Der p 2 and compare it to the hIgE mAb 2F10 epitope in the context of the allergenic structure of Der p 2. X-ray crystallography was used to determine the epitope of anti–Der p 2 hIgE mAb 4C8. Epitope mutants created by targeted mutagenesis were analyzed by immunoassays and in vivo using a human high-affinity IgE receptor (FcεRIα)–transgenic mouse model of passive systemic anaphylaxis. The structure of recombinant Der p 2 with hIgE mAb 4C8 Fab was determined at 3.05 Å. The newly identified epitope region does not overlap with the hIgE mAb 2F10 epitope or the region recognized by 3 overlapping hIgE mAbs (1B8, 5D10, and 2G1). Compared with wild-type Der p 2, single or double 4C8 and 2F10 epitope mutants bound less IgE antibodies from allergic patients by as much as 93%. Human FcεRIα–transgenic mice sensitized by hIgE mAbs, which were susceptible to anaphylaxis when challenged with wild-type Der p 2, could no longer cross-link FcεRI to induce anaphylaxis when challenged with the epitope mutants. These data establish the structural basis of allergenicity of 2 hIgE mAb nonoverlapping epitopes on Der p 2, which appear to make important contributions to the hIgE repertoire against Der p 2 and provide molecular targets for future design of allergy therapeutics. [ABSTRACT FROM AUTHOR]

The aim of the study was to assess the impact of a video training program (VTP) on primary school teachers' skills in using an adrenaline auto-injector (AAI), in correlation with knowledge regarding allergies, in cases of anaphylaxis. A questionnaire on teachers' knowledge of allergies and on their level of confidence in using an AAI was distributed in primary schools in the French department of Manche (2173 teachers). A VTP followed this questionnaire. A second questionnaire was then distributed. Theoretical knowledge was assessed with a score out of 20. The confidence level was rated on a scale from 1 to 4. We collected 218 responses to the first questionnaire (10.0 % of the population included). The response rate to the second questionnaire was 4.7 % (103 participants), and from this group, 93 of the 103 participants viewed the video (90.3 %). Overall, 76 of the 218 (34.9 %) participants who completed the first questionnaire also completed the second questionnaire and watched the VTP. The number of participants who completed the whole survey was 76 (out of 2173, 3.5 %). The VTP significantly improved teachers' knowledge of the subject of allergies (the average score increased by 2.11 points, p < 0.001) as well as their confidence in recognizing the signs of a severe allergic reaction and in using an AAI: 85.4 % (n = 88) of self-confident teachers after the VTP versus 42.3 % (n = 92) before the VTP (p < 0.001). The VTP improved teachers' level of knowledge and confidence in using an AAI in cases of anaphylaxis. A similar VTP could be circulated more widely in schools to offer easy access to training tools about allergies. [ABSTRACT FROM AUTHOR]

Perioperative anaphylaxis is a rare and unpredictable event that continues to cause patient harm. More work is needed to decrease the risk to patients through measures to limit sensitisation, optimise management and investigation, and ensure that patients are not inadvertently re-exposed to allergens. Robust epidemiological data such as that provided by the consecutive GERAP surveys over the past 30 yr have been invaluable in defining the problem, identifying emerging allergens, acting as a catalyst for change, and stimulating research. [ABSTRACT FROM AUTHOR]

Perioperative anaphylaxis is rare but is associated with significant morbidity. This complication has been well described in France by the GERAP (Groupe d'Etude des Réactions Anaphylactiques Périopératoires), a network focused on its study. The epidemiology of perioperative anaphylaxis is evolving, influenced by environmental factors and clinical practice. The aim of this study was to update the epidemiology of perioperative anaphylaxis in France. This multicentre retrospective study was performed in 26 allergy clinics of the GERAP network in 2017–8. There were 765 patients with perioperative anaphylaxis included. Most cases were severe, with 428 (56%) reactions graded as 3 or 4 according to the Ring and Messmer classification. Skin test results were available for 676 patients, with a culprit agent identified in 471 cases (70%). Neuromuscular blocking agents were the main cause of perioperative anaphylaxis (n =281; 60%), followed by antibiotics (n =118; 25%) and patent blue dye (n =11; 2%). Cefazolin was the main antibiotic responsible for perioperative anaphylaxis (52% of antibiotic-related reactions). Suxamethonium and rocuronium were the main neuromuscular blocking agents responsible for perioperative anaphylaxis with 7.1 (6.1–8.4) and 5.6 (4.2–7.4) reactions per 100,000 vials sold, respectively, whereas cefazolin-related cases were estimated at 0.7 (0.5–0.9) reactions per 100,000 vials sold. Our results confirm that most commonly identified triggering agents remain neuromuscular blocking agents. Reactions to antibiotics, particularly cefazolin, are becoming increasingly frequent. The origin of sensitisation to cefazolin is unknown, as no cross-sensitisation has been described, and it should be the subject of further study. Perioperative anaphylaxis should be followed over the years and understood given the changing triggers. ClinicalTrials.gov (NCT 04654923). [ABSTRACT FROM AUTHOR]

• ABO-incompatible liver transplantation often needs therapeutic plasma exchange (TPE). • Our patient experienced an anaphylactic reaction to fresh frozen plasma during TPE. • Successful management was achieved through a multidisciplinary approach. ABO-incompatible living donor liver transplantation (ABOi LDLT) is a complex procedure involving the reduction of anti-A and anti-B antibodies by therapeutic plasma exchange (TPE) to prevent acute antibody-mediated rejection. Fresh frozen plasma (FFP) is often used as replacement fluid during TPE. We report an ABOi LDLT case in which the patient experienced an anaphylactic reaction to FFP during TPE. Additional TPE was performed using 5% albumin as replacement fluid. ABOi LDLT was successfully performed by adapting the transfusion strategy to avoid FFP and cryoprecipitate and to administer washed platelets. This case highlights the importance of careful preoperative assessment, multidisciplinary coordination, and individualized approaches in ABOi LDLT, especially when the patient has an anaphylactic reaction to FFP. [ABSTRACT FROM AUTHOR]

Esophageal thermal injury is one of the most devastating complications of atrial radiofrequency ablation, and its diagnosis can be challenging. In this report, we highlight the novel use of free water as a contrast material to better visualize the esophageal lumen in a patient with anaphylaxis to Iodinated contrast media and Gadolinium who recently underwent atrial fibrillation ablation. This becomes particularly handy in patients with contrast allergy, and further emphasizes the role of multimodality imaging. [Display omitted] • MR hydrography is a novel technique that can be used for evaluation of esophageal perforation after RF ablation procedures. • This technique is useful in a subset of patients with contrast allergy in whom multimodality imaging evaluation is necessary. • This report forms the basis of a new imaging technique that could potentially be used in clinical practice in the future. [ABSTRACT FROM AUTHOR]

The recent approval of omalizumab for the treatment of IgE-mediated food allergy is an important step forward for the millions of food allergy patients in the United States. Through the depletion of circulating IgE and the subsequent reduction of FcεR1 on key effector cells, patients increase their tolerance to food allergens. However, omalizumab does not permit patients to eat foods that they are allergic to with impunity. Rather, it protects them from most accidental exposures. In addition, omalizumab does not cure food allergy and has not demonstrated true immunomodulation. Thus, omalizumab might be a lifelong therapy for some patients. Furthermore, there are many important questions and issues surrounding the appropriate administration of omalizumab to treat food allergy, which we discuss. Managing treatment of patients with disease that falls outside the dosing range, assessing treatment response or nonresponse, addressing its appropriateness for patients older than 55, and determining whether immunotherapy plus omalizumab provides any advantage over omalizumab alone all need to be examined. Identifying appropriate patients for this therapy is critical given the cost of biologics. Indeed, not all food allergy patients are good candidates for this therapy. Also, when and how to stop omalizumab therapy in patients who may have outgrown their food allergy needs to be elucidated. Thus, although this therapy provides a good option for patients with food allergies, much information is needed to determine how best to use this therapy. Despite many unanswered questions and issues, we provide clinicians with some practical guidance on implementing this therapy in their patients. [ABSTRACT FROM AUTHOR]

Despite the promise of oral immunotherapy (OIT) to treat food allergies, this procedure is associated with potential risk. There is no current agreement about what elements should be included in the preparatory or consent process. We developed consensus recommendations about the OIT process considerations and patient-specific factors that should be addressed before initiating OIT and developed a consensus OIT consent process and information form. We convened a 36-member Preparing Patients for Oral Immunotherapy (PPOINT) panel of allergy experts to develop a consensus OIT patient preparation, informed consent process, and framework form. Consensus for themes and statements was reached using Delphi methodology, and the consent information form was developed. The expert panel reached consensus for 4 themes and 103 statements specific to OIT preparatory procedures, of which 76 statements reached consensus for inclusion specific to the following themes: general considerations for counseling patients about OIT; patient- and family-specific factors that should be addressed before initiating OIT and during OIT; indications for initiating OIT; and potential contraindications and precautions for OIT. The panel reached consensus on 9 OIT consent form themes: benefits, risks, outcomes, alternatives, risk mitigation, difficulties/challenges, discontinuation, office policies, and long-term management. From these themes, 219 statements were proposed, of which 189 reached consensus, and 71 were included on the consent information form. We developed consensus recommendations to prepare and counsel patients for safe and effective OIT in clinical practice with evidence-based risk mitigation. Adoption of these recommendations may help standardize clinical care and improve patient outcomes and quality of life. [ABSTRACT FROM AUTHOR]

Systemic allergic reactions (sARs) following coronavirus disease 2019 (COVID-19) mRNA vaccines were initially reported at a higher rate than after traditional vaccines. We aimed to evaluate the safety of revaccination in these individuals and to interrogate mechanisms underlying these reactions. In this randomized, double-blinded, phase 2 trial, participants aged 16 to 69 years who previously reported a convincing sAR to their first dose of COVID-19 mRNA vaccine were randomly assigned to receive a second dose of BNT162b2 (Comirnaty) vaccine and placebo on consecutive days in a blinded, 1:1 crossover fashion at the National Institutes of Health. An open-label BNT162b2 booster was offered 5 months later if the second dose did not result in severe sAR. None of the participants received the mRNA-1273 (Spikevax) vaccine during the study. The primary end point was recurrence of sAR following second dose and booster vaccination; exploratory end points included biomarker measurements. Of 111 screened participants, 18 were randomly assigned to receive study interventions. Eight received BNT162b2 second dose followed by placebo; 8 received placebo followed by BNT162b2 second dose; 2 withdrew before receiving any study intervention. All 16 participants received the booster dose. Following second dose and booster vaccination, sARs recurred in 2 participants (12.5%; 95% CI, 1.6 to 38.3). No sAR occurred after placebo. An anaphylaxis mimic, immunization stress-related response (ISRR), occurred more commonly than sARs following both vaccine and placebo and was associated with higher predose anxiety scores, paresthesias, and distinct vital sign and biomarker changes. Our findings support revaccination of individuals who report sARs to COVID-19 mRNA vaccines. Distinct clinical and laboratory features may distinguish sARs from ISRRs. [ABSTRACT FROM AUTHOR]

Allergen immunotherapy, also called desensitisation, is a strategic process by which the immune system is gradually "trained" to tolerate increasing amounts of an allergen, which it previously would have reacted to. In the UK, it is estimated that approximately 20% of the population suffers with at least one allergic disease. The potential to modify the disease process is no longer out of our reach for certain allergies, with the hope of improved quality of life. Immunotherapy can be offered as a treatment for IgE mediated allergic disease such as allergic rhinoconjunctivitis, immediate type food allergies, bee and wasp anaphylaxis, and can have a synergistic effect on asthma and eczema. However, it would be incorrect to consider this treatment as a panacea, as there remain pitfalls, gaps in equity of treatment, and uncertainty with longer-term efficacy of the newer food desensitisation treatments. This review focuses on our current clinical understanding and indications for immunotherapy for children and young people, delivery and monitoring within the UK, and the future scope of immunotherapy. [ABSTRACT FROM AUTHOR]

• Study assessed four adverse events following 2022–2023 seasonal influenza vaccines. • Study population was 12.7 million Medicare enrollees 65 years and older. • There was no increase in post-vaccination incidence rates for three adverse events. • Anaphylaxis rates were elevated and possibly modified by concomitant vaccination. While safety of influenza vaccines is well-established, some studies have suggested potential associations between influenza vaccines and certain adverse events (AEs). This study examined the safety of the 2022–2023 influenza vaccines among U.S. adults ≥ 65 years. A self-controlled case series compared incidence rates of anaphylaxis, encephalitis/encephalomyelitis, Guillain-Barré Syndrome (GBS), and transverse myelitis following 2022–2023 seasonal influenza vaccinations (i.e., any, high-dose or adjuvanted) in risk and control intervals among Medicare beneficiaries ≥ 65 years. We used conditional Poisson regression to estimate incidence rate ratios (IRRs) and 95 % confidence intervals (CIs) adjusted for event-dependent observation time and seasonality. Analyses also accounted for uncertainty from outcome misclassification where feasible. For AEs with any statistically significant associations, we stratified results by concomitant vaccination status. Among 12.7 million vaccine recipients, we observed 76 anaphylaxis, 276 encephalitis/encephalomyelitis, 134 GBS and 75 transverse myelitis cases. Only rates of anaphylaxis were elevated in risk compared to control intervals. With all adjustments, an elevated, but non-statistically significant, anaphylaxis rate was observed following any (IRR: 2.40, 95% CI: 0.96–6.03), high-dose (IRR: 2.31, 95% CI: 0.67–7.91), and adjuvanted (IRR: 3.28, 95% CI: 0.71–15.08) influenza vaccination; anaphylaxis IRRs were 2.54 (95% CI: 0.49–13.05) and 1.64 (95% CI: 0.38–7.05) for persons with and without concomitant vaccination, respectively. Rates of encephalitis/encephalomyelitis, GBS, or transverse myelitis were not elevated following 2022–2023 seasonal influenza vaccinations among U.S. adults ≥ 65 years. There was an increased rate of anaphylaxis following influenza vaccination that may have been influenced by concomitant vaccination. [ABSTRACT FROM AUTHOR]

Mast cells (MCs) are tissue-resident immune cells, well-positioned at the host-environment interface for detecting external antigens and playing a critical role in mobilizing innate and adaptive immune responses. Sensory neurons are afferent neurons innervating most areas of the body but especially in the periphery, where they sense external and internal signals and relay information to the brain. The significance of MC–sensory neuron communication is now increasingly becoming recognized, especially because both cell types are in close physical proximity at the host-environment interface and around major organs of the body and produce specific mediators that can activate each other. In this review, we explore the roles of MC–sensory neuron crosstalk in allergic diseases, shedding light on how activated MCs trigger sensory neurons to initiate signaling in pruritus, shock, and potentially abdominal pain in allergy, and how activated sensory neurons regulate MCs in homeostasis and atopic dermatitis associated with contact hypersensitivity and type 2 inflammation. Throughout the review, we also discuss how these 2 sentinel cell types signal each other, potentially resulting in a positive feedback loop that can sustain inflammation. Unraveling the mysteries of MC–sensory neuron crosstalk is likely to unveil their critical roles in various disease conditions and enable the development of new therapeutic approaches to combat these maladies. [ABSTRACT FROM AUTHOR]

Despite the purported link between pholcodine and neuromuscular blocking agent allergy, screening for prior pholcodine use offers no practical benefit to patients, and anaesthetists should continue to use a neuromuscular blocking agent where this is clinically indicated. [ABSTRACT FROM AUTHOR]

Histone deacetylase 6 (HDAC6) has been shown to play an important role in allergic inflammation. This study hypothesized that novel downstream targets of HDAC6 would mediate allergic inflammation. Experiments employing HDAC6 knock out C57BL/6 mice showed that HDAC6 mediated passive cutaneous anaphylaxis (PCA) and passive systemic anaphylaxis (PSA). Antigen stimulation increased expression of N-myc (MYCN) and CXCL3 in an HDAC6-dependent manner in the bone marrow-derived mast cells. MYCN and CXCL3 were necessary for both PCA and PSA. The role of early growth response 3 (EGR3) in the regulation of HDAC6 expression has been reported. ChIP assays showed EGR3 as a direct regulator of MYCN. miR-34a-5p was predicted to be a negative regulator of MYCN. Luciferase activity assays showed miR-34a-5p as a direct regulator of MYCN. miR-34a-5p mimic negatively regulated PCA and PSA. MYCN decreased miR-34a-5p expression in antigen-stimulated rat basophilic leukemia cells (RBL2H3). MYCN was shown to bind to the promoter sequence of CXCL3. In an IgE-independent manner, recombinant CXCL3 protein increased expression of HDAC6, MYCN, and β-hexosaminidase activity in RBL2H3 cells. Mouse recombinant CXCL3 protein enhanced the angiogenic potential of the culture medium of RBL2H3. CXCL3 was necessary for the enhanced angiogenic potential of the culture medium of antigen-stimulated RBL2H3. The culture medium of RBL2H3 was able to induce M2 macrophage polarization in a CXCL3-dependent manner. Recombinant CXCL3 protein also increased the expression of markers of M2 macrophage. Thus, the identification of the novel role of HDAC6-MYCN-CXCL3 axis can help better understand the pathogenesis of anaphylaxis. [Display omitted] • Antigen stimulation increases the expression of MYCN in HDAC6-dependent manner. • MYCN mediates anaphylaxis by increasing the expression of CXCL3. • miR-34a directly decreases the expression of MYCN and suppresses anaphylaxis. • CXCL3 induces M2 macrophages polarization and mediates anaphylaxis. • HDAC6-MYCN-CXCL3 axis might be employed for developing anti-allergy drugs. [ABSTRACT FROM AUTHOR]

Epinephrine is the first-line treatment for severe allergic reactions, and rapid treatment is associated with lower rates of hospitalization and death. Current treatment options (epinephrine auto-injectors and manual intramuscular injection) are considered cumbersome, and most patients/caregivers fail to use them, even during severe reactions. An intranasal epinephrine delivery device, neffy , has been designed to provide an additional option for patients/caregivers. We sought to assess the comparative pharmacokinetics and pharmacodynamics of neffy 2.0 mg, EpiPen 0.3 mg, and manual intramuscular injection 0.3 mg. This was a phase 1, randomized, 6-treatment, 6-period, 2-part crossover study in 59 healthy subjects. Pharmacokinetic and pharmacodynamic parameters following single and repeat doses of epinephrine were assessed before dosing and at various postdose intervals. The pharmacokinetic profile of neffy was bracketed by approved injection products, with a mean peak plasma level of 481 pg/mL, which fell between EpiPen (753 pg/mL) and epinephrine manual intramuscular injection (339 pg/mL). When dosed both once and twice, neffy resulted in more pronounced increases in pharmacodynamic parameters relative to EpiPen or manual injection. neffy 's pharmacokinetic profile was bracketed by approved injection products, with pharmacodynamic responses that were comparable to or better than approved injection products. neffy is expected to be a safe and effective option, particularly for patients/caregivers who are reluctant to carry and use injection devices. [ABSTRACT FROM AUTHOR]

We report an unusual case of anaphylaxis induced by the lysozyme-containing over-the-counter-drug Lysopaine®, which contains 20 mg lysozyme hydrochloride and 1.5 mg cetylpyridinium chloride, in a 9-year-old child with allergy to hen's egg as well as multiple IgE-mediated food allergies. The involvement of lysozyme was confirmed by positive skin prick tests for Lysopaine® and the presence of specific IgE against lysozyme. Our case highlights the importance of properly educating allergic patients to recognize allergens, even minor ones. Despite the presence of lysozyme in various food and drug products, it is not necessarily perceived as an allergenic protein by patients with egg allergy, and the labeling may be misleading, thereby exposing patients to potentially severe reactions. [ABSTRACT FROM AUTHOR]

Alpha-gal syndrome (AGS) is an allergy to "red meat" and other mammalian products due to immunoglobulin E (IgE) antibodies against the sugar moiety galactose-alpha-1,3-galactose (alpha-gal), which is acquired following tick bites. Clinically, AGS presents with urticaria, abdominal pain, nausea, and occasionally anaphylaxis, and has wide inter- and intra-personal variability. Because symptom onset is generally delayed by 2 to 6 hours after meat consumption, AGS can be easily confused with other causes of urticaria and anaphylaxis, such as chronic spontaneous urticaria (CSU) and mast cell activation syndrome (MCAS). Diagnosis relies on a combination of clinical history, positive alpha-gal IgE blood testing and improvement on a mammalian-restricted diet. Management of the syndrome centers primarily on avoidance of mammalian meats (and occasionally dairy and other products) as well as acute management of allergic symptoms. Counseling about tick avoidance measures is also important as AGS will wane over time in many patients. [ABSTRACT FROM AUTHOR]

Increased TPSAB1 copy numbers encoding ⍺-tryptase are associated with severe reactions in adults with Hymenoptera venom allergy, systemic mastocytosis, and idiopathic anaphylaxis. The primary objective was to assess the association between ⍺-tryptase and severity of food allergy. A total of 119 subjects underwent tryptase genotyping; 82 of them were from an observational food allergy cohort at the National Institute of Allergy and Infectious Disease (NIAID), and 37 were from a cohort of children who reacted to peanut oral food challenge (OFC) at Lurie Children's Hospital of Chicago. The primary predictor was presence or absence of ⍺-tryptase. The primary outcomes for both cohorts were measures of severity of food allergy reaction. Secondary outcomes included OFC symptom scores (Bock/Practical Allergy [PRACTALL] and Severity Grading Score for Acute Reactions [SGSAR]). Correlation between total α-tryptase isoforms and OFC scores was also assessed to account for gene dosage effects. Among the subjects in the NIAID cohort, the presence of ⍺-tryptase was associated with a higher prevalence of food-triggered anaphylaxis than in those with only β-tryptase (P =.026). Similarly, only 1 of 6 subjects in the OFC cohort with only β-tryptase (17%) had a severe reaction, whereas 20 of 31 of subjects with α-tryptase (65%) had a severe reaction (P =.066). Subjects with ⍺-tryptase also had higher total SGSAR scores than did the subjects with no ⍺-tryptase (P =.003). In addition, there were also significant positive correlations between ⍺-tryptase isoform copy numbers and both higher total SGSAR and Bock/PRACTALL OFC scores (P =.008 and P =.003, respectively). The presence of α-tryptase in subjects is correlated with a higher prevalence of anaphylaxis or severe reaction to food than in subjects without any α-tryptase. [ABSTRACT FROM AUTHOR]

The rate of anaphylaxis following COVID-19 vaccinations is estimated to be 2–11 cases per million doses administered. However, adrenaline is occasionally used in individuals who are later diagnosed with immunisation stress-related responses, as their initial presenting signs and symptoms can appear similar to that of anaphylaxis. This study aims to describe the clinical profile of individuals who had received adrenaline following a COVID-19 vaccine and their subsequent revaccination outcomes. We examined notifications of cases who had received adrenaline following a COVID-19 vaccine in New South Wales, Australia. The cases were classified into Brighton Collaboration Case Definition (BCCD) for anaphylaxis, their clinical presentation, management and subsequent revaccination outcomes were compared. From 22 February 2021 to 30 September 2021, there were 222 cases where adrenaline was administered. Of these, 32 (14 %) fulfilled Level 1 BCCD, 59 (27%) Level 2, 2 (1%) Level 3, 97 (44%) Level 4 and 32 (14 %) Level 5. The most commonly reported symptoms were sensation of throat closure (n = 116, 52%), difficulty breathing (n = 82, 37%) and nausea (n = 55, 25 %). Of the 176 (79%) individuals who proceeded to further vaccination, 89 (51%) received the same vaccine formulation and only 14 (8%) experienced another allergic adverse event with 9 (5%) receiving adrenaline. Less than one in five individuals who received adrenaline met Level 1 BCCD criteria for anaphylaxis. Many reactions that were treated with adrenaline had little to no diagnostic certainty of anaphylaxis and in such cases repeat vaccination had a high likelihood of being tolerated. Increased awareness and education on objective signs and symptoms of anaphylaxis is required to ensure appropriate use of adrenaline. [ABSTRACT FROM AUTHOR]

Tarantula envenomations are encountered infrequently but may increase with increased exotic animal ownership. This case report presents the first documented toxicity from a Venezuelan suntiger tarantula (VST), Psalmopoeus irminia , and provides a general framework for approaching patients with tarantula exposures. A 35-year-old man presented to an emergency department 4 h after experiencing a bite from his pet VST. He developed erythema, pain, and edema to the bite site on the left thenar eminence that extended proximally. Within 4 h, he developed abdominal pain, nausea, vomiting, throat itching, and tightness. The patient had a blood pressure of 131/105 mm Hg, heart rate of 102 beats/min, 36.6°C, respiratory rate of 20 breaths/min, and SpO 2 of 94%. Laboratory evaluations were within normal limits (other than chronically elevated but improved transaminases). The patient received 0.5 mg epinephrine intramuscularly, 50 mg diphenhydramine IV, 20 mg famotidine IV, 0.4 mg ondansetron IV, and 1 L of normal saline for a suspected anaphylactic reaction. Shortly after epinephrine administration, his gastrointestinal and upper airway symptoms resolved. All symptoms resolved within 1 week. Little is known about VST toxicity. Therefore, providers should rely on a general framework for approaching patients with tarantula exposures. Morbidity from tarantula exposures is mediated by mechanical injury, venom effects, and hypersensitivity reactions. Typical clinical findings include local pain, pruritis, edema, erythema, and burning. Muscle cramping, ophthalmia nodosa, and hypersensitivity reactions may occur. Treatment is primarily supportive and includes decontamination, cool compresses, analgesia, treatment of anaphylaxis, and ophthalmology evaluation if ocular exposure. [ABSTRACT FROM AUTHOR]

This guidance updates 2021 GRADE (Grading of Recommendations Assessment, Development and Evaluation) recommendations regarding immediate allergic reactions following coronavirus disease 2019 (COVID-19) vaccines and addresses revaccinating individuals with first-dose allergic reactions and allergy testing to determine revaccination outcomes. Recent meta-analyses assessed the incidence of severe allergic reactions to initial COVID-19 vaccination, risk of mRNA-COVID-19 revaccination after an initial reaction, and diagnostic accuracy of COVID-19 vaccine and vaccine excipient testing in predicting reactions. GRADE methods informed rating the certainty of evidence and strength of recommendations. A modified Delphi panel consisting of experts in allergy, anaphylaxis, vaccinology, infectious diseases, emergency medicine, and primary care from Australia, Canada, Europe, Japan, South Africa, the United Kingdom, and the United States formed the recommendations. We recommend vaccination for persons without COVID-19 vaccine excipient allergy and revaccination after a prior immediate allergic reaction. We suggest against >15-minute postvaccination observation. We recommend against mRNA vaccine or excipient skin testing to predict outcomes. We suggest revaccination of persons with an immediate allergic reaction to the mRNA vaccine or excipients be performed by a person with vaccine allergy expertise in a properly equipped setting. We suggest against premedication, split-dosing, or special precautions because of a comorbid allergic history. [ABSTRACT FROM AUTHOR]

IgE-induced mast cell (MC) degranulation can be inhibited by IgG antibodies, signaling via FcγRIIb, but the effects of IgG on IgE-induced MC transcription are unknown. We sought to assess inhibitory IgG:FcγRIIb effects on MC responses to IgE using complementary transcriptomic and functional approaches. RNA sequencing was performed on bone marrow–derived MCs from wild-type and FcγRIIb-deficient mice to identify genes activated following IgE receptor crosslinking that were further modulated in the presence of antigen-specific IgG in an FcγRIIb-dependent fashion. Parallel analyses of signaling pathways and allergic responses in vivo were performed to assess the impact of these changes in gene expression. Rapid changes in the transcription of 879 genes occurred in MCs activated by IgE, peaking at 1 hour. Surprisingly, only 12% of these were altered by IgG signaling via FcγRIIb, including numerous transcripts involved in orchestrating type 2 responses linked to spleen tyrosine kinase signaling. Consistent with this finding, IgG suppressed IgE-induced phospho-intermediates in the spleen tyrosine kinase signaling pathway. In vivo studies confirmed that the IgG-mediated suppression of both systemic anaphylaxis and MC-driven tissue recruitment of inflammatory cells following allergen challenge was dependent on FcγRIIb. In contrast, genes in the STAT5a cell survival pathway were unaltered by IgG, and STAT5a phosphorylation increased after IgE-induced MC activation but was unaffected by IgG. Our findings indicate that inhibitory IgG:FcγRIIb signals block an IgE-induced proallergic program but spare a prosurvival program. [ABSTRACT FROM AUTHOR]

Adjuvant radiation therapy (RT) affects survival after surgery for young children (age <3 years) diagnosed with intracranial ependymoma. Conformal photon RT promised to spare normal tissue and was introduced more than 25 years ago to improve outcomes for these vulnerable patients. Long-term results for those first treated with conformal methods provide valuable information and serve as a comparison against newer methods. Between 1997 and 2018, 101 patients <3.1-years-old were treated with conformal and intensity modulated photon therapy after definitive surgery for intracranial ependymoma. The median age at RT was 2.1 years and the time from diagnosis to the start of RT was 10 weeks. The extent of resection was gross-total in 82%, and 38% underwent more than 1 attempt at resection. The total prescribed dose was 54 to 59.4 Gy at 1.8 Gy per fraction. The 10-year event-free and overall survivals were 58.5% ± 5.0% and 72.6% ± 4.5%, respectively, with a median follow-up of 18.4 years (range, 4.2-23.3 years). Tumor progression occurred in 34 patients with a median time of 1.6 years. Death occurred in 34 patients from ependymoma (n = 24), secondary malignancy (n = 6), necrosis (n = 2), shunt failure (n = 1), and anaphylactic reaction (n = 1). Twenty-three patients developed a secondary tumor including 6 cases of fatal high-grade glioma. Of the surviving cohort and those ≥18 years old, 98% obtained a high school diploma, 64% had a current driver's license, 89% were students or employed full or part time, 32% were living independently, and 70% received higher education or training. Long-term results of children treated using photon conformal RT after surgery demonstrate that adjuvant RT resulted in long-term disease control and functional independence. These results point to the need for new treatment strategies to improve tumor control and provide investigators hope that newer RT methods will further reduce complications. [ABSTRACT FROM AUTHOR]

• Monitoring the safety of vaccines containing novel adjuvants is important. • Risk of new-onset immune-mediated events after HepB-CpG versus HepB-alum was similar. • The risk of herpes zoster was not increased after HepB-CpG compared with HepB-alum. • No cases of anaphylaxis occurred after receipt of HepB-CpG. • This study did not identify safety concerns of HepB-CpG compared with HepB-alum. HepB-CpG (Heplisav-B) is a licensed hepatitis B vaccine with a novel adjuvant that requires 2 doses (0, 1 month) compared to HepB-alum (Engerix-B) which requires 3 doses (0, 1, 6 months). Monitoring safety outcomes following receipt of vaccines with novel adjuvants outside trial settings is important. Hence, as part of a post-marketing commitment, we compared the incidence of new-onset immune-mediated diseases, herpes zoster (HZ), and anaphylaxis among recipients of HepB-CpG versus HepB-alum. This cohort study included adults not on dialysis who received ≥1 dose of hepatitis B vaccine from 8/7/2018 to 10/31/2019, during which HepB-CpG was routinely administered in 7 of 15 Kaiser Permanente Southern California medical centers while HepB-alum was administered in the other 8 centers. Recipients of HepB-CpG or HepB-alum were followed through electronic health records for 13 months for occurrence of pre-specified new-onset immune-mediated diseases, HZ, and anaphylaxis identified using diagnosis codes. Incidence rates were compared using Poisson regression with inverse probability of treatment weighting when there was ≥80 % power to detect a relative risk (RR) of 5 for anaphylaxis and RR of 3 for other outcomes. Chart review to confirm new-onset diagnosis was conducted for outcomes with statistically significant elevated risk. There were 31,183 HepB-CpG and 38,442 HepB-alum recipients (overall 49.0 % female, 48.5 % age ≥50 years, and 49.6 % Hispanic). Among immune-mediated events that occurred frequently enough for formal comparison, rates among HepB-CpG versus Hep-B-alum recipients were similar except for rheumatoid arthritis (RA) (adjusted RR 1.53 [95 % CI: 1.07, 2.18]). After chart confirmation of new-onset RA, the adjusted RR was 0.93 (0.34, 2.49). The adjusted RR for HZ was 1.06 (0.89, 1.27). Anaphylaxis occurred in 0 HepB-CpG and 2 HepB-alum recipients. This large post-licensure study did not identify evidence of safety concerns for HepB-CpG compared to HepB-alum for immune-mediated diseases, HZ, or anaphylaxis. [ABSTRACT FROM AUTHOR]

We provide a commentary on aspects of a prospective study of the epidemiology of perioperative anaphylaxis in Japan (Japanese Epidemiologic Study for Perioperative Anaphylaxis [JESPA]). Accurate diagnosis of perioperative anaphylaxis is important for research but essential for clinical safety. We evaluate the diagnostic approach used in the JESPA study and caution against over-reliance on diagnostic tests that lack sensitivity and specificity when clinical data suggest an immediate perioperative hypersensitivity reaction is likely. [ABSTRACT FROM AUTHOR]