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Background Objective Methods Results Conclusions Trial Registration Number In Europe, Omalizumab (anti‐IgE) is indicated for the treatment of moderate to severe asthma, but not for IgE‐mediated food allergy (FA).We assessed the impact of Omalizumab on efficacy, safety, and quality of life (FA‐QoL) in patients with moderate to severe asthma and who have a history of anaphylaxis to peanut, tree nuts, fish, egg, milk, and/or wheat.Food‐allergic children (6–18 years) with moderate to severe asthma underwent oral food challenges (OFCs) to establish the threshold of reaction to the culprit food(s) at baseline (T0) and at 4‐month intervals (T1, T2, and T3) during their first year of treatment with Omalizumab. We recorded the number and severity of food‐allergic reactions, Asthma Control Test (ACT) scores, FA‐QoL, and total IgE levels.In 65 patients allergic to 107 foods, the No Observed Adverse Events Level (NOAEL) at T1 increased: 243‐ and 488‐fold for fresh and baked milk, respectively; 172‐ and 134‐fold for raw and baked egg; 245‐fold for hazelnut; 55‐fold for peanut; 31‐fold for wheat; and 10‐fold for fish. Full tolerance was achieved in 66.4% of OFCs at T1, 58.3% at T2, and 75% at T3. Ninety‐five foods were liberalized in the diet of 55 patients; the remaining 12 were introduced by 10 patients at least in traces. Throughout the study, 40 out of 65 were able to get a free diet. ACT increased from 17 (Q1‐Q3: 15–17) to 23.6 (Q1‐Q3: 23–25). The FA‐QoL score in children ≤12 years decreased from 4.63 ± 0.74 to 2.02 ± 1.13, and in adolescents from 4.68 ± 0.92 to 1.90 ± 1.50.During Omalizumab therapy, a safe reintroduction of allergenic foods is feasible.ClinicalTrials.gov, NCT06316414. [ABSTRACT FROM AUTHOR]

IntroductionMethodsResultsDiscussionAnaphylaxis is a globally increasing allergic reaction that is often fatal. Recently, our previous study reported the possibility of using the modified natural products “sodium R-lipoate (NaRLA) and enzymatically modified isoquercitrin (EMIQ)“ as potential novel safe agents against the non-immunological-degranulation of mast cells.Here, we extended our previous findings by determining the antianaphylactic activity of 50 and 100 mg/kg body weight of NaRLA and EMIQ (given orally and prior to local or systemic challenge) in mice models of ovalbumin (OVA)-induced IgE-dependent active cutaneous anaphylaxis (ACA) and active systemic anaphylaxis (ASA) in comparison with sulfasalazine (SSZ, amast cell stabilizer).The pre-treatment of mice with NaRLA or EMIQ completely succeeded, as SSZ, in suppression of the increased vascular permeability associated with IgE-dependent ACA and protected the OVA-sensitized mice from fatal ASA by reducing (p < .001) the skin mast cell degranulation, the elevated peritoneal histamine and interleukin-4 levels, along with decreasing the associated sever gastrointestinal and lung histopathological alterations and inflammation. The high dose of EMIQ prevented death in 70% of mice with anaphylactic shock, better than SSZ.Our data indicated that NaRLA and EMIQ may be potential prophylactic and therapeutic candidates for the alleviation of atopic and systemic anaphylaxis. [ABSTRACT FROM AUTHOR]

Background: Kounis syndrome is defined as the concurrence of acute coronary syndromes in the setting of allergic or anaphylactic reactions. It primarily affects men aged 40–70 years and is often associated with chest pain. This syndrome is often unrecognized and undiagnosed in clinical practice due to a low level of awareness. Herein, we present a case of type I Kounis syndrome in a young woman without chest pain. Case presentation: A 28-year-old Japanese woman with a history of atopic dermatitis received a glycyrrhizin, glutathione, and neurotropin preparation (a preparation of inflamed skin extract from rabbits inoculated with vaccinia virus) at a dermatology clinic to treat pruritus caused by atopic dermatitis. Immediately after the administration, the patient developed abdominal pain and generalized body wheals. The patient was diagnosed with anaphylaxis and was transported to our hospital. She had no chest pain on arrival at our hospital; however, a 12-lead electrocardiogram showed ST elevation in leads I, aVL, V2, and V3, and an echocardiogram showed decreased wall motion in the anterior and lateral walls of the left ventricle. Sublingual nitroglycerin administration improved ST-segment elevation and left ventricular wall motion abnormalities. The patient underwent emergency coronary angiography, which revealed no significant stenosis, and was diagnosed with type I Kounis syndrome. Conclusion: Kounis syndrome without chest pain is rare in young women. Since it can be fatal in cases with severe allergic symptoms such as anaphylaxis, the possibility of concurrent acute coronary syndrome should be considered when treating systemic allergic reactions, regardless of age, sex, or the presence or absence of chest symptoms. [ABSTRACT FROM AUTHOR]

Objective: Anaphylaxis is a life-threatening reaction characterized by sudden symptoms affecting different organ systems, and healthcare professionals must recognize and urgently treat anaphylaxis. In this study, we aimed to evaluate the knowledge and attitudes of family physicians in Türkiye about the diagnosis and treatment of anaphylaxis, use of adrenaline auto-injector, and factors affecting these attitudes. Methods: This was a cross-sectional descriptive survey study. An online questionnaire was administered to family physicians to evaluate their knowledge levels regarding the diagnosis and treatment of anaphylaxis and the use of AAI. Results: The study was completed with 207 participants, mean age was 33.8±8.5 years and mean professional experience was 8.5±8.3 years. 93.7% of the participants stated that the first-line treatment of anaphylaxis was adrenaline, 85.5% the correct route of adrenaline administration was intramuscular, 79.2% the right place of adrenaline administration, 75.4% the dose of adrenaline in children, 61.8% of them answered the adrenaline dose correctly in adults. 51.2% of the participants stated that they knew about the use of AAI, and 24.6% had received training on this subject. The average number of professional years of participants who knew that the first-line treatment was adrenaline, the correct route and place of administration of adrenaline, and knew how to use auto-injectors were statistically significantly lower (p=0.031, p<0.001, p<0.001, p=0.041, respectively). Family physicians who received post-graduation training on anaphylaxis; the rate of knowing that the first-line treatment of anaphylaxis was adrenaline, the correct route and place of administration of adrenaline, and the rate of knowing the use of auto-injectors were statistically significantly higher (p=0.013, p=0.037, p=0.024, p=0.011, respectively). Conclusion: The most significant outcome of our study is family physicians' knowledge of the diagnosis and treatment of anaphylaxis is higher when their training at medical faculty and specialist training is more recent and when they undergo post-graduation training. With post-graduation training programs, family physicians can become more competent in life-threatening anaphylaxis. However, physicians' knowledge of adrenaline auto-injector therapy is insufficient. Family physicians should be trained on the use of this essential and life-saving drug for those at risk of anaphylaxis. [ABSTRACT FROM AUTHOR]

Background: Urticaria is a common disease with a marked influence on quality of life. The key cell involved is the mast cell, which can be activated by a vast variety of stimuli, and the major mediator is histamine. Allergic urticaria is a disorder with a large variety of causes: food, drugs, insect venom, skin contact with allergens, and physical exercise. Buckwheat consumption has increased in European countries and the USA because it is gluten-free. It can trigger anaphylactic shock if ingested, inhaled, or handled with the hands. Five common buckwheat allergens named Fag e1 to 5 (Fag e1, 2, and 3 are considered the major allergens) and two tartary buckwheat allergens named Fag t1 and Fag t2 have been described. Method: We present the case of a patient who experienced two anaphylactic shocks and in whom the etiological factor was buckwheat. The patient presented to the Allergology department for the evaluation of two episodes of severe allergic reactions that required emergency therapy, episodes that involved the loss of consciousness and were of major severity. At each anaphylactic shock, an ambulance was requested, and emergency therapy was administered, leading to the patient's recovery within a few hours. Diagnosis: Since each episode occurred a few minutes after eating, the diagnosis was established based on a detailed anamnesis and prick skin tests, followed by specific IgE dosages. Other foods consumed by the patient, assessed by prick skin testing and specific IgE dosages of suspected foods, were excluded as the etiological cause. Increased levels of buckwheat-specific immunoglobulin E were highlighted, thus identifying the etiological agent. The treatment of anaphylactic shock was performed urgently by the ambulance crew with adrenaline, infusion solutions, cortisone preparations, and antihistamines. Result: Following the treatment that was initiated, there was a partial remission of the lesions after a few hours. Conclusions: Buckwheat allergy is rare, but it produces symptoms that affect the skin, gastrointestinal tract, and respiratory tract, as well as anaphylaxis. In a professional environment, it can trigger allergic rhinitis, asthma, and hives. Although buckwheat allergens have been described, their clinical relevance has only been studied in a small number cases. In current practice, the only commercially available allergen is Beech e2 per the ImmunoCAP ISAC microarray. Diagnosis can be difficult in clinical practice. This reported case suggests the need for a thorough anamnesis, since buckwheat is consumed as a hidden allergen, and in Europe, it is not necessary to label foods containing this allergen. [ABSTRACT FROM AUTHOR]

SonoVue (Bracco, Milan, Italy) is a drug used in ultrasonography for the purpose of increasing the echogenicity of blood or fluids by improving the signal-to-noise ratio. Background/Objectives/Methods: We described a case of anaphylaxis due to SonoVue and performed a literature review. Results and Conclusions: We reported a case of anaphylaxis secondary to the administration of SonoVue and described all the 13 literature cases. Given its widespread use and the potentially dangerous nature of the reactions it can cause, it is advisable to know how to promptly recognize fatal reactions. [ABSTRACT FROM AUTHOR]

This article discusses the role of IL-33, an alarmin cytokine, in regulating mast cell responses during food allergy. The IL-33 receptor, ST2, is expressed on mast cells, and genetic variations in the IL-33/ST2 axis are associated with disease susceptibility. The study used a mouse model of food allergy and found that IL-33 is critical for inducing mast cell responses to food antigens. Mice lacking ST2 showed decreased diarrhea, mast cell accumulation, and mast cell activation compared to wild-type mice. The study also found that IL-4 plays a role in mediating mast cell responses, as treatment with IL-4 reversed the attenuated mast cell activation in ST2-deficient mice. These findings provide insights into the potential interplay between IL-33 and IL-4 in the treatment of allergic diseases. [Extracted from the article]

Background: In patients who require venom immunotherapy (VIT), there is a need to identify underlying mast cell (MC) disorders since these may affect the risk and severity of future sting reactions and the long‐term effectiveness of VIT. Methods: 1319 individuals with Hymenoptera venom allergy (HVA) who needed VIT from referral centers in Slovenia, Austria, Croatia, and Poland underwent examination for KIT p.D816V in peripheral blood leukocytes (PBL) using a highly sensitive PCR test and tryptase genotyping by digital droplet PCR. We also included 183 control individuals with large local reactions (LLRs) to Hymenoptera stings and with asymptomatic sensitization to Hymenoptera venoms. Results: 285 of 1319 individuals recommended for VIT (21.6%) were positive for KIT p.D816V in PBL, preferably those who present with severe reaction (33.9% [n = 207 of 610] with Ring‐Messmer grade 3–4 vs. 11% [n = 78 of 709] with Grade 1–2; p <.0001), whereas only 1.3% (n = 2 of 152) of controls with LLR and none with asymptomatic sensitization (n = 31) had KIT p.D816V. KIT p.D816V allelic burden was higher in those with severe reaction (median 0.018% [n = 207] in Grade 3–4 vs. 0.001% [n = 78] in Grade 1–2; p <.0001), and the majority had normal baseline serum tryptase levels (69% [n = 196 of 285]). All KIT p.D816V‐positive individuals (n = 41) who underwent bone marrow (BM) biopsy were found to have underlying clonal diseases, principally BM mastocytosis. HαT was also associated with severe HVA and symptoms (p <.01), and remarkably, 31.0% (n = 31 of 100) were found to have concomitant KIT p.D816V. Concomitant HαT and KIT p.D816V showed an additive effect, and having both was associated with the highest risk for severe HVA, even higher than having either HαT or KIT p.D816V alone (OR = 3.8; p <.01). Conclusions: By employing prospective universal tryptase genotyping and examination for KIT p.D816V in PBL in large HVA populations, we have demonstrated a high burden of clonal MC disorders and HαT in patients who require VIT. [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]

Food-dependent exercise-induced anaphylaxis (FDEIA) is an uncommon but potentially life-threatening condition characterized by allergic reactions triggered by the combination of specific food ingestion and physical exertion. Despite its rarity, FDEIA poses significant diagnostic and management challenges due to its complex pathophysiology and variable clinical presentation. Diagnosis relies on careful evaluation of clinical history, symptomatology, and laboratory tests, with inherent difficulties in distinguishing FDEIA from other related conditions. Management of FDEIA involves comprehensive strategies to minimize the risk of allergic reactions through measures such as allergen avoidance, patient education, and timely administration of epinephrine. While existing treatment approaches primarily target acute reactions, ongoing research endeavors are crucial for validating emerging diagnostic and therapeutic modalities. This review offers a comprehensive overview of FDEIA, encompassing its epidemiology, underlying pathophysiology, clinical presentations, diagnostic challenges, and management approaches. [ABSTRACT FROM AUTHOR]

Purpose: Acute allergic reactions may occur in susceptible individuals following exposure to various allergens. Obesity is linked to allergic reactions, and weight loss from bariatric surgery may attenuate the severity of certain conditions such as airway hyperresponsiveness in asthma. This retrospective observational study investigates associations between prior bariatric surgery and lower risk for life-threatening conditions in patients hospitalized with acute allergic reactions and anaphylaxis. Materials and Methods: Adults ≥ 18 years old diagnosed with morbid obesity and admitted to US hospitals with acute allergic reactions/anaphylaxis were included. All data were extracted from the US Nationwide Inpatient Sample (NIS) database 2005–2018. Patients without information on in-hospital mortality, discharge destination, hospital costs, and length of stay (LOS) were excluded. Patients were divided into two groups based on prior bariatric surgery or not. All diagnoses were verified through ICD-9 and ICD-10 codes. Between-group differences and associations between variables were evaluated using logistic regression analysis. Results: After matching, patients with prior bariatric surgery had significantly lower proportions of any life-threatening morbidity (37.2% vs. 47.4%), respiratory distress or failure (11.2% vs. 17.0%), pneumonia or severe infection (7.4% vs. 10.2%), sepsis/septic shock (15.2% vs. 20.9%), intubation and mechanical ventilation (11.2% vs. 14.6%), prolonged LOS (10.3% vs. 20.6%) and unfavorable discharge (6.9% vs. 12.5%) than those without prior bariatric surgery. Conclusion: Prior bariatric surgery predicts a lower risk of life-threatening morbidity and prolonged LOS among adults hospitalized for acute allergic reaction and anaphylaxis. Future prospective studies are warranted to confirm the present findings and reveal underlying mechanisms. [ABSTRACT FROM AUTHOR]

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Immunoglobulin E (IgE) plays pivotal roles in allergic diseases through interaction with a high-affinity receptor (FcεRI). We established that Fab fragments of anti-IgE antibodies (HMK-12 Fab) rapidly dissociate preformed IgE-FcεRI complexes in a temperature-dependent manner and inhibit IgE-mediated anaphylactic reactions, even after allergen challenge. X-ray crystallographic studies revealed that HMK-12 Fab interacts with each of two equivalent epitopes on the Cε2 homodimer domain involved in IgE F(ab')2. Consequently, HMK-12 Fab-mediated targeting of Cε2 reduced the binding affinity of Fc domains and resulted in rapid removal of IgE from the receptor complex. This unexpected finding of allosteric inhibition of IgE-FcεRI interactions by simultaneous targeting of two epitope sites on the Cε2 homodimer domain of IgE F(ab')2 may have implications for the development of novel therapies for allergic disease. The authors show that the allosteric inhibition of the interactions between Immunoglobulin E and the high-affinity receptor FcεRI by targeting two epitope sites of IgE may have implications for the development of novel therapies for allergic diseases. [ABSTRACT FROM AUTHOR]

The article provides an update on the diagnosis and treatment of alpha-Gal syndrome, a red meat allergy caused by specific antibodies. The syndrome is severe and associated with delayed anaphylaxis, and it is not directly linked to tick-borne infections. Diagnosis involves a combination of history, sensitization tests, and oral challenges. Management includes avoiding alpha-Gal exposure, but serious reactions can still occur. Oral immunotherapy shows promise but requires further study. The document itself is a list of authors, affiliations, and references related to alpha-gal syndrome and meat allergy. [Extracted from the article]

Sinomenine hydrochloride (SH) is commonly used in the treatment of rheumatoid arthritis. It activates mast cells and induces anaphylaxis in the clinical setting. Adverse drug reactions can be caused by activation of MAS-associated G proteincoupled receptor X2 (MRGPRX2) on mast cells. Because the ligand binding site of MRGPRX2 is easily contacted in dilute solvents, it can be activated by many opioid drug structures. N-Demethylsinomenine (M-3) has a similar chemical structure to that of the opioid scaffold and is a major metabolite of SH. We sought to clarify whether M-3 induces anaphylaxis synergistically with its prototype in a mouse model. Molecular docking computer simulations suggested a similar binding effect between M-3 and SH. M-3 was chemically synthesized and analyzed by surface plasmon resonance to reveal its affinity for MRGPRX2. Temperature monitoring, in vivo hindlimb swelling and exudation test, and in vitro mast cell degranulation test were used to explore the mechanism of MRGPrx2 mediated allergic reaction triggered by M-3. Reduced M-3-induced inflammation was evident in MrgprB2 (the ortholog of MRGPRX2) conditional (Cpa3-Cre/MrgprB2flox) knockout (MrgprB2-CKO) mice. Additionally, LAD2 human mast cells with MRGPRX2 knockdown showed reduced degranulation. M-3 activated LAD2 cells synergistically with SH as regulated by GRK2 signaling and IP3R/PLC/PKC/P38 molecular signaling pathways. The results indicate that the M-3 metabolite can activate mast cells synergistically with its prototype SH via MRGPRX2 and aggravate anaphylaxis. These findings provide important insights into drug safety. [ABSTRACT FROM AUTHOR]

Idiopathic anaphylaxis (IA) remains a frustrating challenge for both patients and physicians. The aim of this paper is to focus on IA in pediatric ages and suggest possible diagnostic algorithms according to specific age ranges (infants, children, and adolescents). In fact, in a variable percentage of patients, despite extensive diagnostic tests, the cause of anaphylactic episodes cannot be identified. Moreover, the lack of a unanimous IA definition requires a careful and detailed diagnostic workup. Prompt recognition of signs and symptoms, especially in younger children, and an accurate clinical history often allow a choice of the most appropriate diagnostic tests and a correct differential diagnosis. [ABSTRACT FROM AUTHOR]

Background: The skin-prick and intradermal tests are the main diagnostic methods used to identify the causative agent in patients with suspected perioperative anaphylaxis. Although the intradermal test is more sensitive than the skin-prick test, multiple intradermal injections can be painful for children. Here, we present the case of a child with autism and suspected perioperative anaphylaxis. The causative agent was successfully identified using the intradermal test under general anesthesia. Case presentation: An 8-year-old boy with autism developed anaphylaxis during general anesthesia for the fourth cleft lip and palate surgery. An allergic workout was performed, but both the skin-prick and basophil activation tests for suspected causative agents yielded negative results. The patient was afraid of multiple injections, and an intradermal test was performed under general anesthesia by anesthesiologists and allergists. Piperacillin was confirmed as the causative agent, and subsequent surgery using the same anesthetic agents without piperacillin was uneventful. Conclusions: Concerted efforts should be made to identify the causative agent for diagnosing perioperative anaphylaxis. [ABSTRACT FROM AUTHOR]

Human fibrinogen (FIB) has been clinically proven to be considerably effective for the treatment of postoperative bleeding, with reported cases of allergic reactions to human FIB being rare. Here, we report a case of an anaphylactic shock in 27-year-old patients with rheumatic heart valve disease who received a human FIB infusion during mitral valve replacement, aortic valve replacement, and tricuspid valve-shaping surgery. The patients showed generalised profuse sweating, a barely noticeable skin rash, faint pulse, systolic pressure < 50 mmHg, and a heart rate of 71 beats/min. We share insights from a case of severe allergy to human FIB infusion during cardiac surgery, through which we have gained experience in the processes of diagnosing and treating. This report aims to provide a preliminary summary of the characteristics of this case to serve as a reference for fellow clinicians. [ABSTRACT FROM AUTHOR]

A randomized, active-controlled, double-blind, first-in-human, phase 1 study was conducted in healthy Korean adults to evaluate the safety, tolerability, and immunogenicity of EuNmCV-5, a new pentavalent meningococcal vaccine targeting serogroups A, C, W, X, and Y. Sixty participants randomly received a single dose of either EuNmCV-5 or MenACWY-CRM, a quadrivalent vaccine containing serogroups A, C, W, and Y. Safety was assessed through monitoring anaphylactic reactions, adverse events for 28 days, and serious adverse events over 180 days. Immunogenicity was assessed via rabbit complement-dependent serum bactericidal antibody (rSBA) assay. EuNmCV-5 was safe, well-tolerated, and elicited a substantial antibody titer increase. The seroprotection rates exceeded 96.7%, and the seroconversion rates were over 85% for all the targeted serogroups. It showed higher seroconversion rates against serogroups A and C (p = 0.0016 and 0.0237, respectively) and elicited a substantial increase in GMT for all targeted serogroups compared to the MenACWY-CRM. ClinicalTrials.gov identifier: NCT05739292. [ABSTRACT FROM AUTHOR]

Background: Neuromuscular blocking agents (NMBAs) are primarily used during surgical procedures to facilitate endotracheal intubation and optimize surgical conditions. This study aimed to explore the adverse event signals of NMBAs, providing reference for clinical safety. Methods: This study collected reports of atracurium, cisatracurium, rocuronium, and vecuronium as primary suspect drugs in The US Food and Drug Administration Adverse Event Reporting System (FAERS) from the first quarter of 2004 to the third quarter of 2023. The adverse events (AEs) reported in the study were retrieved based on the Preferred Terms (PTs) of the Medical Dictionary for Regulatory Activities. In addition, we conducted disproportionality analysis on relevant reports using the reporting odds ratio (ROR) method and Bayesian confidence propagation neural network (BCPNN) method. A positive signal was generated when both algorithms show an association between the target drug and the AE. Results: A total of 11,518 NMBA-related AEs were reported in the FAERS database. The most AEs of rocuronium were collected. NMBA-related AEs involved 27 different system organs (SOCs), all of the four NMBAs had positive signals in “cardiac disorders,” “immune system disorders,” “respiratory, thoracic and mediastinal disorders” and “vascular disorders.” At the PTs level, a total of 523 effective AEs signals were obtained for the four NMBAs. AEs labled in the instructions such as anaphylaxis (include anaphylactic reaction and anaphylactic shock), bronchospasm, respiratory arrest and hypotension were detected positive signals among all NMBAs. In addition, we also found some new AEs, such as ventricular fibrillation for the four NMBAs, hyperglycaemia for atracurium, kounis syndrome and stress cardiomyopathy for rocuronium, hepatocellular injury for cisatracurium, hyperkalaemia for vecuronium. To further investigated the AEs associated with serious clinical outcomes, we found that cardiac arrest and anaphylaxis were the important risk factors for death due to NMBAs. Conclusion: NMBA-related AEs have a significant potential to cause clinically severe consequences. Our study provides valuable references for the safety profile of NMBAs, and considering the limitations of the FAERS database, further clinical data are needed to validate the findings of this study. [ABSTRACT FROM AUTHOR]

The effect of polysaccharides isolated from the aboveground parts of Saussurea salicifolia (L.) DC on Th2 type immune response reactions was studied. Administration of water-soluble polysaccharides presented by arabino-galacturonans (weight average molecular weight 158.49 kDa) to mice against the background of experimental Th2 immunity reduced the severity of anaphylactic and local immediate type hypersensitivity reactions. It also suppressed the production of ovalbumin-specific IgE and IgG1 and increased the stability of mast cell membranes. The studied polysaccharide complex increased IFNγ secretion and inhibited IL-4 synthesis. These findings suggest that these polysaccharides may be considered as potential anti-allergic agents that suppress the development of allergy in its early stages. [ABSTRACT FROM AUTHOR]

Rectal drug formulations (RDFs) are used for local and systemic treatments. In addition to their therapeutic use, they are also be used in the diagnostic evaluations of lower and upper gastrointestinal system diseases. RDFs can lead to the development of earlytype hypersensitivity reactions, even anaphylaxis. On the other hand, early-type hypersensitivity reactions following rectal enema administration are extremely rare in children. Here, two pediatric cases are presented where one developed urticaria and angioedema, and the other experienced anaphylaxis, immediately after rectal enema administration for the treatment of constipation. In this case report, through a literature review with two pediatric cases, we believe that we draw attention to the potential early-type hypersensitivity reactions that may develop with rectal enemas, which are frequently used in daily practice. [ABSTRACT FROM AUTHOR]

Anaphylaxis typically occurs due to immunological mechanisms involving IgE, IgG, or complement-mediated responses, but nonimmunological mechanisms can also contribute to the development of anaphylaxis by triggering mast cell and basophil degranulation. In cases where alternative treatment options are unavailable, or when the use of a specific drug is essential, a desensitization protocol should be considered. In this context, we present a successful oral desensitization protocol in a pediatric patient who experienced anaphylaxis after taking acetazolamide orally. [ABSTRACT FROM AUTHOR]

Objective: This study aims to assess the level of knowledge of doctors on anaphylaxis and its management at a tertiary care teaching hospital. Materials and Methods: A pretested structured questionnaire was administered to the doctor, assistant doctor, and specialist doctor. Volunteers were asked to answer a questionnaire containing questions about anaphylaxis and its management. The questionnaire was administered face to face. Results: Physicians from different branches of surgery and internal medicine participated in the study together with general practitioners, and the average age of 85 physicians participating in the study was 42.6 years. In the study, 8 of those participating were general practitioners, twenty six were medical residency students, and fifty one were working as specialist physicians in the tertiary hospital. The majority of the participants (83.5%) stated that they had encountered anaphylaxis before. There was no statistical difference between professional experience and the anaphylaxis encounter rate (p=0.76). Only 4 participants correctly answered the diagnostic criteria of anaphylaxis. While 85% of the participants marked the combination of skin and respiratory signs and symptoms for the diagnosis, only 15% marked the combination of cardiovascular and gastrointestinal system signs and symptoms for the diagnosis. Unfortunately twenty participants did not administer intramuscular (im) adrenaline as first-line therapy in the treatment of anaphylaxis. After anaphylactic shock, sixty nine participants stated that the patient should be kept under observation for 8 to 24 hours. Conclusion: Knowledge regarding anaphylaxis and its management is a basic requirement that every health care provider must acquire for the appropriate treatment of all patients. We show that there was no statistical relationship between professional experience and the diagnosis and treatment of anaphylaxis. We think that it would be beneficial to provide physicians with in service training regarding the diagnosis and management of anaphylaxis. [ABSTRACT FROM AUTHOR]

Oxaliplatin serves as a basic therapeutic agent for various malignant tumors. Oxaliplatin-induced hypersensitivity reactions are potentially life-threatening, and frequently lead to treatment discontinuation. Alternative therapies may be less effective and/or more expensive, with varying tolerability. Oxaliplatin hypersensitivity reactions typically manifest as a classic type I allergy, as well as cytokine release reactions and mixed types. In clinical practice, management of anaphylaxis and questions relative to rechallenge with oxaliplatin after occurrence of hypersensitivity reactions are of utmost concern. Therefore, based on evidence-based medicine and clinical practice experience, the expert panel carried out a comprehensive assessment and discussion on the definition, clinical characteristics, diagnosis, classification and grading criteria, management, and rechallenge of hypersensitivity reactions to oxaliplatin. Eventually, the "Chinese expert consensus on whole-process management of oxaliplatin-induced hypersensitivity reactions (2024 edition)" was formulated to further standardize the whole-process management of oxaliplatin-induced hypersensitivity reactions. The consensus has been registered on Practice guideline REgistration for transPAREncy (PREPARE) with the registration number PREPARE-2024CN371. [ABSTRACT FROM AUTHOR]

Allergic diseases affect up to 40% of the global population with a substantial rise in food allergies, in particular, over the past decades. For the majority of individuals with allergy fundamental programming of a pro-allergic immune system largely occurs in early childhood where it is crucially governed by prenatal genetic and environmental factors, including their interactions. These factors include several genetic aberrations, such as filaggrin loss-of-function mutations, early exposure to respiratory syncytial virus, and various chemicals such as plasticizers, as well as the influence of the gut microbiome and numerous lifestyle circumstances. The effects of such a wide range of factors on allergic responses to an array of potential allergens is complex and the severity of these responses in a clinical setting are subsequently not easy to predict at the present time. However, some parameters which condition a pro-allergic immune response, including severe anaphylaxis, are becoming clearer. This review summarises what we currently know, and don’t know, about the factors which influence developing pro-allergic immunity particularly during the early-life perinatal period. [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]

This article explores the emergence of lupin as a potential hidden food allergen. The true prevalence of lupin allergy is currently unknown, but the Allergy-Vigilance Network® (AVN) reported 62 cases of lupin-induced anaphylaxis out of 2,708 cases of food-induced anaphylaxis from 2002 to 2020. The study found that lupin-induced anaphylaxis was more common in females, adults, individuals with a peanut allergy, and after consuming prepacked food products. The research also revealed a significant degree of cross-reactivity between lupin and other legumes, particularly peanut. The authors recommend that allergists be aware of lupin cross-reactivity and that patients with a history of food anaphylaxis be tested for lupin. [Extracted from the article]

Certain chemotherapy agents have an increased potential to cause allergic reactions. These reactions can vary in severity from mild to severe, and a change in treatment may be suggested for the patient to avoid the causative agent going forward. This can lead to suboptimal treatment and a change from first-line therapy to a second-line therapy. In certain scenarios, drug desensitization may be considered to allow for continued administration of a standard-of-care chemotherapy agent to cure or palliate a patient's cancer. [ABSTRACT FROM AUTHOR]

Introduction: In 15–35 percent of patients with anaphylaxis, the triggering allergen cannot be found; therefore, a diagnosis of idiopathic anaphylaxis (IA) is made. We report on the outcomes in patients with IA treated with omalizumab. Methods: We included consequent omalizumab-treated IA adult patients treated with omalizumab 300 mg every 4 weeks. Results: Out of 7 patients, 6 were female, median age 40 years with the frequency of anaphylaxis episodes from 3 in 2 years to 5 in 4 months. Baseline tryptase ranged from 1.71 to 12.0 μg/L. An increase in tryptase during anaphylaxis was documented in 6 patients. Activating KIT p.D816V variant was detected in 2 patients. One patient also had hereditary alpha-tryptasemia (HαT). The duration of omalizumab treatment was 0.5–7.5 years. None of the patients have experienced an anaphylactic reaction since the start of treatment. Mild systemic reactions were reported in 6 patients (86%). The presence of underlying cMCD had no impact on the treatment outcome. Conclusion: All patients in our study had complete responses to omalizumab. The presence of KIT p.D816V and HαT did not influence the response to omalizumab treatment. [ABSTRACT FROM AUTHOR]

Background: Anaphylaxis represents the most severe end of the spectrum of allergic reactions. Frequent elicitors of anaphylaxis are insects, foods, and drugs. This paper summarizes recent development with regard to emerging and novel elicitors of anaphylaxis. Summary: Food allergens on the rise include pulses (like pea, chickpea), seeds (hemp, chia), nuts (cashew), pseudograins (buckwheat, quinoa), fruits, and microalgae. Novel foods are foods that were not consumed to any significant extent in the European Union before May 1997, which includes four edible insects (mealworm, migratory locust, house cricket, and buffalo worm). Recent investigations have pointed out the risk of anaphylaxis associated with the consumption of yellow mealworm for people allergic to shellfish and house dust mites. In Europe, fire ants (mostly Solenopsis invicta) and Vespa velutina nigrithorax represent invasive species, which account for increasing numbers of anaphylactic reactions. Also, several new drugs, especially biologicals, have been associated with anaphylaxis. Key Messages: Elicitors of anaphylaxis are changing as a result of (i) increase in demand for plant-based food, (ii) introduction of novel foods, (iii) spreading of allergens by climate changes and globalization, or (iv) due to exposure to newly developed drugs. [ABSTRACT FROM AUTHOR]