Anaphylactic Patients Research Articles

Evaluating Practice Patterns of Observation Periods Following Epinephrine Administration for Anaphylaxis Among Pediatric Patients.

Objective Current guidelines recommend that anaphylactic patients be observed for 4-6 hours following epinephrine administration to monitor for biphasic reactions. There is conflicting data regarding the efficacy of these guidelines and the prevalence of biphasic reactions among the pediatric population. This retrospective study aimed to investigate the appropriateness of these guidelines through evaluation of observation periods and patterns of biphasic reaction development among pediatric anaphylactic patients at a single-institution ED. Methods Patients less than 18 years of age who presented to the ED of a tertiary academic medical center between 2017 and 2022 and were treated with epinephrine for anaphylaxis were included in the study. The frequency and timing of biphasic reactions were observed. Duration of ED observation, time between symptom onset and first dose of epinephrine, number and category of anaphylactic symptoms, and allergen type were compared between patients who did and did not experience a biphasic reaction. Additional variables analyzed included persistence of anaphylactic symptoms, additional doses of epinephrine, and adjuvant medications. Contingency tables and two-sample t-tests were used to compare categorical and continuous variables, respectively, between those who did and did not develop a biphasic reaction. Results A total of 292 patients met the inclusion criteria and were included in the analysis. All patients were observed in the ED for a mean of 233.1 minutes. Ten patients (3.4%) developed a biphasic reaction. Six had a reaction within 150 minutes of initial symptom resolution, and four developed one after discharge, within 10 to 33 hours following symptom resolution. There was no significant difference in the length of time observed in the ED (p=0.98) or from symptom onset to the first epinephrine dose (p=0.90) between groups. Presenting with respiratory symptoms was associated with persistent anaphylactic symptoms despite epinephrine administration (p=0.01). Patients with symptoms involving at least two organ systems were 3.45 times more likely to experience persistent symptoms post-epinephrine than those with involvement of only one organ system (OR=3.45; CI: 1.28-9.30). Allergen type, anaphylactic symptoms, or the number of organ systems involved were not linked to developing a biphasic reaction or the need for additional epinephrine doses. Conclusions The patients who developed a biphasic reaction did so either shortly following initial symptom resolution or many hours past the recommended observation period. Extending the observation period of patients within reasonable parameters would not have reduced the number of patients who experienced a biphasic reaction after discharge. The results of this study support potentially adopting a more individualized approach to anaphylaxis management following epinephrine administration. Shortening the observation period for patients at low risk for biphasic reactions could reduce the patient burden on EDs without negatively impacting patient outcomes. Although no significant risk factors for biphasic reactions were identified in this study, closer monitoring of patients with respiratory symptoms and/or involvement of a greater number of organ systems may help mitigate the number of patients who experience persistence of anaphylaxis despite treatment.

COVID-19 vaccines: anaphylaxis and anxiety : Acase study from an allergy unit.

Vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) was one crucial element to overcome the coronavirus disease 2019 (COVID-19) pandemic. Even though anaphylaxis to vaccines is rare, 47patients came to the Allergy Unit at the University Hospital Graz, Austria, reporting immediate anaphylactoid symptoms after administration of COVID-19 vaccines. In addition, 29patients with known drug-induced anaphylaxis wanted to be tested for apossible sensitization against COVID-19 vaccines or excipients, such as polyethylene glycol (PEG) or polysorbate80 (PS80) before the first COVID-19 vaccination. Skin prick tests and intradermal tests were performed in all 76patients, mostly using PEG 2000, and/or PS80. Skin prick tests with COVID-19 vaccines were performed depending on availability. Our aim was to characterize this patient cohort in terms of patients' anaphylactoid responses, their willingness to future vaccinations against SARS-Cov‑2, and reasons for their decision. We developed aquestionnaire and analyzed 34completed copies. Of the 47patients with anaphylactoid reactions to COVID-19 vaccination, most were female (40female/7male). The skin tests, even when performed with the respective COVID-19 vaccine, were negative in all but one patient. Most patients who experienced anaphylactoid reactions after aCOVID-19 vaccination, did not want another COVID-19 vaccination at the time of answering the questionnaire because of anxiety for another anaphylactoid response at the next shot. Premedication with antihistamines significantly lowered (n = 74vaccinations) the severity of anaphylactoid responses after COVID-19vaccinations. Anxiety about another anaphylactoid episode hinders patients to be vaccinated against SARS-CoV‑2 again. Premedication with antihistamines and collaboration of allergologists with psychologists might lower the risk of an anaphylactic/anaphylactoid response as well anxiety in drug-induced anaphylactic patients.

Descriptive Profile of Anaphylactic Reaction Patients Hospitalized at RSUP Prof. DR. I.G.N.G Ngoerah Period 2018-2023

Introduction: Anaphylactic reaction is a severe, potentially life-threatening systemic hypersensitivity reaction caused by a specific allergen. This study aimed to evaluate the clinical profile of anaphylactic patients hospitalized in Prof. Dr. I.G.N.G. Ngoerah Hospital, Denpasar. Method: This was a cross-sectional descriptive study of anaphylactic patients hospitalized in our center from January 2018 to December 2023. Patients diagnosed with anaphylactic reactions were included in this study. All the data (demographic, clinical manifestations, potential trigger) were attained from medical records for descriptive analysis. Result: 292 patients were enrolled in this study; half were women (54,4%), and the median age was 38,50 years (interquartile range 24). The most common potential triggers were drugs (57%), followed by food (18,5%), blood products (14,1), insect bites, and other triggers (4,8%). Almost all patients experience skin and mucosal manifestations (99%). Anaphylactic shock occurs in only 22% of patients. Discussion: Previous studies have found similar results to our findings, and anaphylactic reaction caused by drugs was associated with a more severe reaction. The effect of estrogen hormones on more severe reactions has been reported in female mice, but human research is still limited. Conclusion: Further studies are needed to investigate the correlation between demographic characteristics or specific clinical manifestations with a severe reaction.

Anaphylaxis: first clinical presentation, subsequent referral practise, and suspected elicitor—an observational study

Anaphylaxis is an allergic manifestation characterised by rapid onset and progression. Rapid treatment may be challenging in patients with atypical symptoms or no previous history of anaphylaxis. This study aimed to describe the clinical prehospital presentation of first-time anaphylactic patients. To help target educational initiatives, we sought to identify which groups of medical professionals are most likely to encounter first-time anaphylactic patients and investigated the referral pattern for suspected anaphylactic patients for specialised treatment. A retrospective register-based study from the Region of Southern Denmark. Patients referred to the Allergy Centre, Odense University Hospital, from 2019 to 2021 were included. The medical records were manually reviewed for first contact with the emergency departments or the emergency medical service. 444 patients with suspected anaphylaxis were referred. 226 patients had grade 3–5 systemic allergic reactions as classified by the World Allergy Organisation; 90% had cutaneous symptoms, 63% symptoms from the central nervous system, 42% gastrointestinal symptoms, 40% cardiovascular symptoms, 36% had upper-airway symptoms, and 36% had lower-airway symptoms. Patients treated prehospitally had a significantly more severe degree of anaphylaxis than patients only treated within the hospital. More than half of the patients with suspected anaphylaxis were referred to the Allergy Centre from the emergency departments. Patients with allergies progressing to severe anaphylaxis most often are treated prehospitally before transport to emergency departments. From the emergency departments, they are referred to the allergy centre. Education concerning the immediate treatment of severe anaphylaxis should primarily be targeted towards prehospital care providers.

The role of molecular diagnosis in anaphylactic patients with dual or triple-sensitization to Hymenoptera venoms

BackgroundThe poly-sensitization to Hymenoptera venom makes it difficult to select genuine allergens for immunotherapy and increases patients’ costs. The objective of this study was to determine the culprit allergen in dual or triple-sensitized patients to three Hymenoptera venoms through molecular diagnosis and evaluating the results of incorporating the molecular diagnosis with skin tests.MethodsThirty-two patients with anaphylactic reactions and dual or triple-sensitization to Hymenoptera venoms in skin tests entered this study. IgE-sensitization to whole extracts and molecules of Apis mellifera (Api m), Vespula vulgaris (Ves v), and Polistes dominulus (Pol d) was evaluated utilizing ALEX or ImmunoCAP.ResultsTwenty-nine patients (90.6%) were male. IgE-sensitization to at least one of the allergenic molecules related to Apis mellifera, Vespula vulgaris, and Polistes dominulus was seen in 59.4, 53.1, and 21.9%, respectively. Among 32 patients, 14 (43.8) and 8 (25%), were mono-sensitized to Api m and Ves v components in ALEX, respectively. Double sensitization to Hymenoptera was identified in 18.8% of patients in ALEX. Api m 1+/Api m 2−/Api m 10− and Ves v 1+/Ves v 5+ demonstrated the most prevalent sensitizations patterns in our patients.ConclusionsThe molecular diagnosis of IgE-sensitization to Hymenoptera venoms can be valuable, especially in patients who show dual or triple-sensitization in skin tests, as the ALEX results revealed mono and double-sensitization to Hymenoptera venoms in 22 and 6 patients, respectively. Regarding the high cost and adverse reactions of venom immunotherapy, especially for two or three venoms, incorporating the molecular diagnosis alongside skin tests for accurate diagnosis of the culprit venom could help decrease costs for patients.

Prehospital and In-Hospital Treatment with Adrenaline and Related Prognosis in Anaphylaxis Patients

Introduction: Although intramuscular adrenaline is the recommended first-line treatment for anaphylaxis, not all patients receive this treatment. The consequences in daily clinical practice are sparsely described. This study aimed to investigate the treatment administered to anaphylactic patients and the related prognosis. Methods: A retrospective register-based study of patients with anaphylaxis referred to the allergy centre, Odense University Hospital (2019–2021). Each patient’s medical records were reviewed for contacts with the emergency departments and the prehospital emergency medical service in the Region of Southern Denmark. The World Allergy Organization (WAO) grading system was used to assess the severity of prehospital and in-hospital anaphylaxis. Furthermore, the treatment administered to the patients was registered. Results: In total, 315 patients were included. The prehospital system had contact with 256 of these patients (two were released prehospitally following treatment and 12 patients had insufficient data to assess anaphylaxis). Of the remaining 242 patients, 115 had anaphylaxis prehospitally (WAO grades 3–5); 59% (67/115) received adrenaline. Among the 67 patients who received prehospital adrenaline, 9 patients (13.4%; 95% CI: 6.3–24.0%) still had anaphylaxis at arrival at the emergency department. Of the 48 patients that were not treated with prehospital adrenaline, 17 patients (35.5%; 95% CI: 22.1–50.5) had anaphylaxis at the arrival to the emergency department. Among the 127 patients without prehospital anaphylaxis (WAO grades 0–2), 22 patients (18.2%; 95% CI: 11.8–26.2%) who did not receive prehospital adrenaline had anaphylaxis at arrival to the emergency department, while none of the 6 patients treated prehospitally with adrenaline had anaphylaxis. Conclusion: Omission of prehospital adrenaline in anaphylactic patients is associated with more severe anaphylactic symptoms at arrival to the hospital. Adrenaline treatment remains suboptimal since only half of the patients received prehospital adrenaline and only 1 out of 4 patients, with clinical signs of anaphylaxis, received adrenaline inside the hospital.

292 The referral pattern and clinical presentation of first-time anaphylactic patients

292 The referral pattern and clinical presentation of first-time anaphylactic patients

Prolonged life-threatening anaphylaxis to Floseal during partial nephrectomy: A case report

Abstract Floseal Hemostatic Matrix is a topical hemostatic agent used across specialties and commonly applied to the renal bed during partial nephrectomy. Here we present the first adult case of Floseal allergy in the literature and the second case of a topical gelatin hemostatic agent. A 62-year-old man underwent partial nephrectomy for a Bosniak type IV cyst. After unclamping the kidney, the patient declined precipitously, later determined due to an anaphylactic reaction to the Floseal placed on the renal bed. The patient had a prolonged anaphylactic reaction that required ionotropic support for over 24 h, possibly due to continued exposure. His tryptase level was elevated, and allergy testing revealed an allergy to the gelatin matrix component of the Floseal. Floseal anaphylaxis should be considered during episodes of cardiovascular collapse after drug administration. However, consideration should be given to removing it to prevent continued exposure and weighed against the risk of prolonged surgery in an anaphylactic patient.

Investigation of the underuse of adrenaline (epinephrine) and prognosis among patients with anaphylaxis at emergency department admission.

Anaphylaxis is a potentially fatal condition; in severe cases of anaphylaxis, the cardiovascular system is often heavily involved. Adrenaline (epinephrine) is a cornerstone of the initial treatment of anaphylaxis. The use of epinephrine remains below expectations in clinical practice. Whether the underuse of epinephrine affects the prognosis of patients with anaphylaxis is still unclear. This retrospective study included patients with anaphylaxis between 2011 and 2020 who were admitted to an emergency department (ED) in Taiwan. All patients were divided into two groups based on the use of epinephrine (or not), and we compared the demographic characteristics, allergens, clinical manifestations, management, and patient outcomes. We reviewed the records of 314 subjects (216 males, 98 females; mean age: 52.78 ± 16.02 years) who visited our ED due to anaphylaxis; 107 (34.1%) and 207 (65.9%) patients were categorized into the epinephrine use group and the non-epinephrine use group, respectively. Arrival via ambulance (p = 0.019), hypotension (p = 0.002), airway compromise (p < 0.001) and altered consciousness (p < 0.001) were the deciding factors for epinephrine use among anaphylactic patients in the ED. The epinephrine use group had higher rates of other inotropic agent usage and fluid challenge. More than 90% of patients received bed rest, steroids, antihistamines, and monitoring. The epinephrine use group had a longer ED length of stay (387.64 ± 374.71 vs. 313.06 ± 238.99 min, p = 0.03) and a greater need of hospitalization. Among all severe symptoms, hypotension was the most tolerated decision factor for not using epinephrine. In this retrospective analysis, some patients with serious anaphylaxis did not experience adverse outcomes or death even without the use of epinephrine at ED admission. Emergent care focuses first on the airway, breathing, and circulation (ABC) and may compensate for the underusage of epinephrine. This could be the reason why epinephrine was underused among patients with anaphylaxis in the ED. In summary, early ABC management continues to play an important role in treating patients with severe anaphylaxis, even when epinephrine is not immediately available in clinical scenarios.

Identification of the biological processes, immune cell landscape, and hub genes shared by acute anaphylaxis and ST-segment elevation myocardial infarction.

Background: Patients with anaphylaxis are at risk for ST-segment elevation myocardial infarction (STEMI). However, the pathological links between anaphylaxis and STEMI remain unclear. Here, we aimed to explore shared biological processes, immune effector cells, and hub genes of anaphylaxis and STEMI. Methods: Gene expression data for anaphylactic (GSE69063) and STEMI (GSE60993) patients with corresponding healthy controls were pooled from the Gene Expression Omnibus database. Differential expression analysis, enrichment analysis, and CIBERSORT were used to reveal transcriptomic signatures and immune infiltration profiles of anaphylaxis and STEMI, respectively. Based on common differentially expressed genes (DEGs), Gene Ontology analysis, cytoHubba algorithms, and correlation analyses were performed to identify biological processes, hub genes, and hub gene-related immune cells shared by anaphylaxis and STEMI. The robustness of hub genes was assessed in external anaphylactic (GSE47655) and STEMI (GSE61144) datasets. Furthermore, a murine model of anaphylaxis complicated STEMI was established to verify hub gene expressions. The logistic regression analysis was used to evaluate the diagnostic efficiency of hub genes. Results: 265 anaphylaxis-related DEGs were identified, which were associated with immune-inflammatory responses. 237 STEMI-related DEGs were screened, which were involved in innate immune response and myeloid leukocyte activation. M0 macrophages and dendritic cells were markedly higher in both anaphylactic and STEMI samples compared with healthy controls, while CD4+ naïve T cells and CD8+ T cells were significantly lower. Enrichment analysis of 33 common DEGs illustrated shared biological processes of anaphylaxis and STEMI, including cytokine-mediated signaling pathway, response to reactive oxygen species, and positive regulation of defense response. Six hub genes were identified, and their expression levels were positively correlated with M0 macrophage abundance and negatively correlated with CD4+ naïve T cell abundance. In external anaphylactic and STEMI samples, five hub genes (IL1R2, FOS, MMP9, DUSP1, CLEC4D) were confirmed to be markedly upregulated. Moreover, experimentally induced anaphylactic mice developed impaired heart function featuring STEMI and significantly increased expression of the five hub genes. DUSP1 and CLEC4D were screened as blood diagnostic biomarkers of anaphylaxis and STEMI based on the logistic regression analysis. Conclusion: Anaphylaxis and STEMI share the biological processes of inflammation and defense responses. Macrophages, dendritic cells, CD8+ T cells, and CD4+ naïve T cells constitute an immune cell population that acts in both anaphylaxis and STEMI. Hub genes (DUSP1 and CLEC4D) identified here provide candidate genes for diagnosis, prognosis, and therapeutic targeting of STEMI in anaphylactic patients.

Investigating the optimal diagnostic value of histamine for diagnosing perioperative hypersensitivity: a prospective, observational study.

Although several guidelines recommend measuring blood tryptase and histamine concentrations to diagnose perioperative anaphylaxis (POA), tryptase measurement is more common. The appropriate timing of blood collection and the diagnostic threshold for histamine measurement are still controversial. To address these issues, histamine concentrations in patients with anaphylaxis and those with anaphylaxis-uncertain were compared in our previous study, the Japanese Epidemiologic Study for Perioperative Anaphylaxis (JESPA). However, because we could not rule out the possibility that the anaphylactic-uncertain group included anaphylactic patients, histamine concentrations were measured in patients who underwent general anesthesia with no complications as controls in the present study. Histamine levels were measured at anesthesia induction (baseline), 30min (first point), and 2h (second point) after the start of surgery in 30 control patients. Histamine concentrations in controls were lower than in patients with POA in JESPA at the first and second points. At the first point, a threshold of 1.5ng/ml resulted in sensitivity of 77% and specificity of 100%. A threshold of 1.1ng/ml at the second point resulted in sensitivity of 67% and specificity of 87%. Measurement of histamine concentrations within two hours after symptom onset might help diagnose POA.

Food anaphylaxis diagnostic marker compilation in machine learning design and validation.

Traditional food allergy assessment of anaphylaxis remains limited in accuracy and accessibility. Current methods of anaphylaxis risk assessment are costly with low predictive accuracy. The Tolerance Induction Program (TIP) for anaphylactic patients undergoing TIP immunotherapy produced large-scale diagnostic data across biosimilar proteins, which was used to develop a machine learning model for patient-specific and allergen-specific anaphylaxis assessment. In explanation of construct, this work describes the algorithm design for assignment of peanut allergen score as a quantitative measure of anaphylaxis risk. Secondarily, it confirms the accuracy of the machine learning model for a specific cohort of food anaphylactic children. Machine learning model design for allergen score prediction utilized 241 individual allergy assays per patient. Accumulation of data across total IgE subdivision served as the basis of data organization. Two regression based Generalized Linear Models (GLM) were utilized to position allergy assessment on a linear scale. The initial model was further tested with sequential patient data over time. A Bayesian method was then used to improve outcomes by calculating the adaptive weights for the results of the two GLMs of peanut allergy score prediction. A linear combination of both provided the final hybrid machine learning prediction algorithm. Specific analysis of peanut anaphylaxis within one endotype model is estimated to predict the severity of possible anaphylactic reaction to peanut with a recall of 95.2% on a dataset of 530 juvenile patients with various food allergies, including but not limited to peanut allergy. Receiver Operating Characteristic analysis yielded over 99% AUC (area under curve) results within peanut allergy prediction. Machine learning algorithm design established from comprehensive molecular allergy data produces high accuracy and recall in anaphylaxis risk assessment. Subsequent design of additional food protein anaphylaxis algorithms is needed to improve the precision and efficiency of clinical food allergy assessment and immunotherapy treatment.

The Timely Administration of Epinephrine and Related Factors in Children with Anaphylaxis.

Anaphylaxis is a severe allergic reaction that requires immediate recognition and intervention. This study investigated the factors related to the timely administration of epinephrine in cases of pediatric anaphylaxis. We performed a retrospective chart review of 107 patients who visited a pediatric emergency center with anaphylaxis between 2015 and 2017. In total, 76 patients received epinephrine injections. We analyzed factors including allergy history, anaphylaxis signs and symptoms, allergen sensitization, anaphylaxis triggers, and time of epinephrine injection. Anaphylactic patients who received epinephrine took a median of 50 min to arrive at the hospital, and patients who did not receive epinephrine took a median of 94 min. Epinephrine administration was significantly delayed by more than 60 min from symptom onset in patients <2 years old. Patients presenting with wheezing symptoms or history of bronchial asthma were significantly more likely to receive epinephrine within 60 min of symptoms onset, while patients with food allergen sensitization were significantly more likely to receive epinephrine within 30 min of hospital arrival. Wheezing, history of asthma, age (≥2 years old), food triggers, and food allergen sensitivity were significant factors for the rapid administration of epinephrine. An immediate diagnosis of anaphylaxis and a rapid administration of epinephrine are essential.

Anaphylaxis in Omani Patients: A Study from a Tertiary Care Center.

ObjectivesAnaphylaxis is an acute and potentially fatal allergic reaction. No studies have yet been conducted to evaluate the spectrum of anaphylactic reactions among Omani patients. As such, this study aimed to describe the clinical features, causes, investigation, and management of anaphylaxis among patients presenting to a tertiary care center in Oman.MethodsThis retrospective study took place between August 2005 and June 2020 at the allergy and immunology clinic of Sultan Qaboos University Hospital, Muscat, Oman. All patients diagnosed with anaphylaxis during the study period were included. Data were collected from electronic medical records.ResultsOne hundred patients were diagnosed with anaphylaxis during the study period. Of these, 52.0% were male. The mean age was 15.9±16.2 years, with 70.0% aged < 18 years old. The eosinophil count ranged from 0.0–16.9 × 109/L, with a mean of 0.8±2.2 × 109/L and a median of 0.3 (0.1–0.6) × 109/L. Total immunoglobulin (Ig) E levels ranged from 25–8706 kIU/L, with a mean of 935.1±1369.5 kIU/L and a median of 500.4 (186.0–972.5) kIU/L. The majority of patients had a family history of allergies (72.0%), and other had concomitant allergic conditions (66.0%). All were prescribed epinephrine (100%). The most common cause of anaphylaxis was food (65.0%). The second most frequent trigger was insect venom (32.0%). Most patients had one category cause (81.0%); two or more causes were present in 12.0% of patients. Clinical symptoms manifested most frequently as cutaneous (92.0%) and respiratory (85.0%). The majority of patients (87.0%) demonstrated the involvement of more than one bodily system. Mean total IgE levels were significantly higher in patients with concomitant presence of other allergic conditions (1193.8 kIU/L) than patients without another concomitant allergic disease (503.6 kIU/L; p =0.030). In addition, concomitant allergic disease is significantly higher in patients < 18 years of age (75.4%) compared to patients > 18 years of age (45.2%; p =0.010).ConclusionsDue to its life-threatening nature, knowledge of the epidemiology and clinical features of anaphylaxis in different populations is necessary to deliver rapid treatment. This study found that the clinical features of anaphylactic patients in Oman were similar to those reported elsewhere. Further research is needed to determine the true incidence of anaphylaxis in Oman to minimize associated morbidity and mortality.

Proteomic and Biological Analysis of an In Vitro Human Endothelial System in Response to Drug Anaphylaxis.

Anaphylaxis is a life-threatening systemic hypersensitivity reaction. During anaphylaxis, mediator release by effector cells causes endothelial barrier breakdown, increasing vascular permeability and leakage of fluids, which may lead to tissue edema. Although endothelial cells (ECs) are key players in this context, scant attention has been paid to the molecular analysis of the vascular system, and further analyses of this cell type are necessary, especially in humans. The protein expression pattern of human microvascular ECs was analyzed in response to sera from anaphylactic patients (EC-anaphylaxis) and sera from non-allergic subjects (EC-control) after 2 hours of contact. Firstly, a differential quantitative proteomic analysis of the protein extracts was performed by mass spectrometry using an isobaric labeling method. Second, the coordinated behavior of the identified proteins was analyzed using systems biology analysis (SBA). The proteome of the EC-anaphylaxis system showed 7,707 proteins, of which 1,069 were found to be significantly altered between the EC-control and EC-anaphylaxis groups (p-value < 0.05). Among them, a subproteome of 47 proteins presented a high rate of change (|ΔZq| ≥ 3). This panel offers an endothelial snapshot of the anaphylactic reaction. Those proteins with the highest individual changes in abundance were hemoglobin subunits and structural support proteins. The interacting network analysis of this altered subproteome revealed that the coagulation and complement systems are the main biological processes altered in the EC-anaphylactic system. The comprehensive SBA resulted in 5,512 functional subcategories (biological processes), 57 of which were significantly altered between EC-control and EC-anaphylaxis. The complement system, once again, was observed as the main process altered in the EC system created with serum from anaphylactic patients. Findings of the current study further our understanding of the underlying pathophysiological mechanisms operating in anaphylactic reactions. New target proteins and relevant signaling pathways operating in the in vitro endothelial-serum system have been identified. Interestingly, our results offer a protein overview of the micro-EC-anaphylaxis environment. The relevance of the coagulation, fibrinolytic, contact and complement systems in human anaphylaxis is described. Additionally, the untargeted high-throughput analysis used here is a novel approach that reveals new pathways in the study of the endothelial niche in anaphylaxis.

The association between neutrophil-to-lymphocyte ratio and anaphylaxis refractory to epinephrine treatment

Objectives: Anaphylaxis refractory to epinephrine treatment is a potentially fatal condition requiring additional medications. Neutrophil-to lymphocyte ratio (NLR) is commonly used to predict severity in allergic diseases. The aim of this study was to determine the association between NLR and refractory anaphylaxis. Methods: This was a retrospective, observational study of 126 adult anaphylaxis patients arriving at the emergency department between January 2015 and December 2019. Patients were placed into refractory anaphylaxis, if they required more than two 0.3 mg injections of intramuscular epinephrine for symptom resolution, and non-refractory anaphylaxis groups. NLRs were determined at the time of arrival at the hospital and were compared between groups. Results: Thirty-two (25.4%) patients were categorized as refractory anaphylaxis cases. NLR was significantly lower in the refractory anaphylaxis than in the non-refractory anaphylaxis group (P &lt; 0.001). In the multivariate logistic regression analysis model, NLR was inversely associated with the occurrence of refractory anaphylaxis (adjusted odds ratio 0.33, 95% confidence interval 0.13-0.81, P = 0.016). The area under the receiver operating characteristic curve of NLR for prediction of refractory anaphylaxis was 0.717 (P &lt; 0.001). The optimal cut-off value of NLR was &lt; 0.68 using the Youden index, with 50.0% sensitivity and 80.9% specificity. Conclusions: NLR was independently and inversely associated with the occurrence of refractory anaphylaxis among anaphylactic patients. Therefore, NLR has the potential to be used as an easy and inexpensive test to predict refractory anaphylaxis in patients.

Safety of yellow fever vaccine administration in confirmed egg-allergic patients

Yellow fever vaccine (YFV) is recommended in endemic areas but represents a risk for egg-allergic patients, as it is cultivated in embryonated eggs. This study aims to describe the outcomes of yellow fever vaccination in patients with confirmed egg allergy (EA). Methods:A prospective study was conducted from January 2018 to September 2019. EA was diagnosed through positive oral food challenge (OFC), recent history of anaphylaxis following egg contact (anaphylaxis in the last 6 months) or immediate allergic reaction in the last 2 months with positive specific IgE. A skinprick test (SPT) with YFV was performed. If the SPT was negative, an intradermal test (ID) was performed at a 1:100 dilution. If the ID was negative, a full dose of YFV was administered. If the skin prick test or ID were positive, the YFV was administered using a graded dosing protocol. Results: It was included 58 patients with confirmed egg allergy (36 M:22F), with a median age of 2.3 years (0.7–13.9 y/o). Forty-two patients had a positive OFC. Nine reported recent anaphylaxis. The other 7 had reactions in the last 2 months with positive specific IgE. During OFC, 15 presented anaphylaxis, while the other 27 presented hives and/or angioedema or vomiting. SPT with YFV was negative in all patients. ID was negative in 48 patients who uneventfully received a full dose of YFV. Ten patients had a positive ID and received YFV in graded doses. Six patients presented a mild reaction controlled with antihistamines, and 4 patients received the vaccine without reactions. Positive ID was significantly related to the vaccine reaction (p < 0.0001). Administration of YFV using a specific protocol was safe even in anaphylactic patients. However, we recommend performing the ID, which can help predict a higher risk of vaccine reaction. An appropriate setting is required to control adverse events.

Anaphylaxis in primary care: Systematic review to support quality of management and optimization of health-care pathways

Anaphylaxis is a severe, life-threatening systemic hypersensitivity reaction characterized by rapid onset and the potential to endanger life. Most of cases of anaphylaxis are first seen by general practitioners (GPs) or emergency doctors. This systematic review is intended to provide evidence-based decision support tools to GPs confronted with anaphylactic patients. We searched MEDLINE, EMBASE, Cochrane Controlled Register of Trials, Lilacs databases from inception from 1988, for manuscripts concerning anaphylaxis and primary care, without language restrictions. We screened studies, extracted data, and assessed risk of bias independently in duplicate. The manual review was performed by two independent ratters. The degree of inter-rater agreement was assessed using Cohen’s kappa. Main outcomes included clinical history, clinical examination, treatment, use of epinephrine and timing to refer the patient to the specialist. We selected 56 studies, comprising 37 original articles, 15 reviews and 4 guidelines. Twenty-three (41%) were focused on specific aetiology: food-induced anaphylaxis (FA) (52%), drug allergy (DA) (35%) and venom allergy (VA) (13%). With a kappa value of 0.67, there was a high agreement on the classification procedures between the two raters. Data showed that in the presence of respiratory and/or cardiovascular symptoms, patients should be promptly treated and sent to the emergency room. Structured clinical history was reported as being mandatory for the diagnosis of anaphylaxis, mainly based on 5 key points: type of manifestations, type of trigger, chronology between reaction and suspected allergen, reproducibility and risk factors. Most documents (44%) covered food-induced anaphylaxis occurring in childhood, with suspected IgE-mediated reaction. Most anaphylaxis in adults were related to DA or VA (48%). Data still stress lack of the recognition of manifestations (48%), treatment with anti-histamines and systemic corticosteroids (26%), delayed application of epinephrine (35%) and highlight the need of decision aids to support diagnosis and anaphylaxis by GPs (38%). GPs should advise an emergency plan and prescribe adrenaline auto-injectors. Reasons for referring to specialists based on the literature are: to investigate aetiology, to undergo specific treatment, such as allergen immunotherapy, severe cases or in suspicion of underlying condition, such as mastocytosis. Evidence presented supports the construction of a decision tree in order to improve management of anaphylaxis. This intends to optimize the life-time of these patients across the health care pathways and prevent avoidable deaths. It is intended that the resultant decision support tool will undergo field-testing for validation.

Safety of yellow fever vaccine administration in confirmed egg-allergic patients

The yellow fever vaccine (YFV) is recommended in endemic areas but represents a risk for egg-allergic patients, as it is cultivated in chicken embryos. This study aims to describe the outcomes of yellow fever vaccination in patients with confirmed egg allergy (EA). Prospective study in a quaternary hospital, from January 2018 to September 2019. EA was diagnosed through oral food challenge (OFC) or recent history of anaphylaxis following egg contact (anaphylaxis in the last 6 months) or allergic reaction in the last 2 months with positive specific IgE. Skin prick test (SPT) with YFV was performed in all participants. If negative SPT, an intradermal test (ID) was performed at 1:100 dilution. If negative ID, a full dose of YFV was administered. If positive skin test, the YFV was administered using a graded-dose protocol. Among 100 patients with prior EA history, 58 were confirmed (36M:22F), median age of 2.35y (0,7 a 13,9Y). Forty-two patients had a positive OFC. Nine reported recent anaphylaxis. The other 7 had reaction in the last 2 months with positive specific IgE. During OFC, 15 presented anaphylaxis and the other (27) presented urticaria and/or angioedema or vomiting. SPT with YFV was negative in all patients. ID was negative in 48 patients, who received a full dose of YFV in usual manner, uneventfully. Ten patients had a positive ID and received the YFV in graded doses, six of them presented a mild reaction controlled with antihistamines and four patients received the vaccine without reactions. Positive ID was significantly related to vaccine reaction (p=0,0001). Administration of YFV using a specific protocol was safe even in anaphylactic patients. We only recommend performing the ID test which contributed to predicting a higher risk of vaccine reaction. An appropriate setting is required in order to control adverse events.

Egg Allergy: Diagnosis and Immunotherapy.

Hypersensitivity or an allergy to chicken egg proteins is a predominant symptomatic condition affecting 1 in 20 children in Australia; however, an effective form of therapy has not yet been found. This occurs as the immune system of the allergic individual overreacts when in contact with egg allergens (egg proteins), triggering a complex immune response. The subsequent instantaneous inflammatory immune response is characterized by the excessive production of immunoglobulin E (IgE) antibody against the allergen, T-cell mediators and inflammation. Current allergen-specific approaches to egg allergy diagnosis and treatment lack consistency and therefore pose safety concerns among anaphylactic patients. Immunotherapy has thus far been found to be the most efficient way to treat and relieve symptoms, this includes oral immunotherapy (OIT) and sublingual immunotherapy (SLIT). A major limitation in immunotherapy, however, is the difficulty in preparing effective and safe extracts from natural allergen sources. Advances in molecular techniques allow for the production of safe and standardized recombinant and hypoallergenic egg variants by targeting the IgE-binding epitopes responsible for clinical allergic symptoms. Site-directed mutagenesis can be performed to create such safe hypoallergens for their potential use in future methods of immunotherapy, providing a feasible standardized therapeutic approach to target egg allergies safely.