Adverse Events Following COVID-19 Vaccination in Adolescents: Insights From Pharmacovigilance Study of VigiBase.

BACKGROUND: During coronavirus disease 2019 (COVID-19) pandemic, several COVID-19 vaccines were licensed with fast-track procedures. Although these vaccines have demonstrated high immunogenicity, there has been concerns on the serious adverse events (AEs) following COVID-19 vaccination among adolescents. We aimed to analyze comparative safety of COVID-19 vaccination in adolescents. METHODS: In this pharmacovigilance study, we performed a disproportionality analysis using VigiBase, the World Health Organization's global individual case safety report (ICSR) database. To compare serious AEs reported following COVID-19 vaccines vs. all other vaccines in adolescents aged 12-17 years, ICSRs following any vaccines on adolescents aged 12-17 years were included, defining cases as reports with the AEs of interest, with all other AEs as non-cases. The AEs of interest were myocarditis/pericarditis, multisystem inflammatory syndrome/Kawasaki disease (MIS/KD), anaphylaxis, Guillain-Barré syndrome (GBS), and immune thrombocytopenia (ITP). We conducted a disproportionality analysis to estimate reporting odds ratio (ROR) with 95% confidence interval (CI) for each AE of interest, adjusted for sex by using logistic regression. RESULTS: Of 99,735 AE reports after vaccination in adolescents, 80,018 reports were from COVID-19 vaccinated adolescents (52.9% females; 56.3% America). The AEs of interest were predominantly reported as serious AE (76.1%) with mRNA vaccines (99.4%). Generally, higher reporting odds for the AEs were identified following COVID-19 vaccination in adolescents; myocarditis/pericarditis (2,829 reports for the COVID-19 vaccine vs. 35 for all other vaccines, adjusted ROR [aROR], 19.61; 95% CI, 14.05-27.39), and MIS/KD (104 vs. 6, aROR, 4.33; 95% CI, 1.89-9.88). The reporting odds for anaphylaxis (515 vs. 165, aROR, 0.86; 95% CI, 0.72-1.02), GBS (94 vs. 40, aROR, 0.64; 95% CI, 0.44-0.92) and ITP (52 vs. 12, aROR, 1.12; 95% CI, 0.59-2.09) were not significantly higher following COVID-19 vaccination. CONCLUSION: In this study, there were disproportionate reporting of immune-related AEs following COVID-19 vaccination. While awaiting definitive evidence, there is a need to closely monitor for any signs of immune-related AEs following COVID-19 vaccination among adolescents.

Fatal food anaphylaxis in adults and children.

Anaphylaxis is a life-threatening reaction characterized by the acute onset of symptoms involving different organ systems and requiring immediate medical intervention. The incidence of fatal food anaphylaxis is 0.03 to 0.3 million/people/year. Most fatal food-induced anaphylaxis occurs in the second and third decades of life. The identified risk factors include the delayed use of epinephrine, the presence of asthma, the use of recreational drugs (alcohol, nicotine, cannabis, etc.), and an upright position. In the United Kingdom (UK) and Canada, the reported leading causal foods are peanuts and tree nuts. In Italy, milk seems to be the most common cause of fatal anaphylaxis in children < 18 years. Fatal food anaphylaxis in Italian children and adolescents almost always occurs outside and is characterized by cardiorespiratory arrest; auto-injectable adrenaline intramuscular was available in few cases. Mortality from food anaphylaxis, especially in children, is a very rare event with stable incidence, but its risk deeply impacts the quality of life of patients with food allergy and their families. Prevention of fatal food anaphylaxis must involve patients and their families, as well as the general public, public authorities, and patients' associations.

COVID-19 vaccine safety: Background incidence rates of anaphylaxis, myocarditis, pericarditis, Guillain-Barré Syndrome, and mortality in South Korea using a nationwide population-based cohort study.

BACKGROUND: To properly assess an association between vaccines and specific adverse events requires a comparison between the observed and background rates; however, studies in South Korea are currently limited. Therefore, in this study, we estimated the background incidence of anaphylaxis, myocarditis, pericarditis, Guillain-Barré syndrome (GBS), and mortality in South Korea. METHODS: A retrospective cohort study was conducted using the National Sample Cohort (NSC) data. Using NSC, the background incidence rate was estimated by dividing the number of episodes during 2009-2019 by the total population by year and then multiplying by 100,000. Using Statistics Korea data, the background mortality rate was estimated by dividing the number of deaths, during 2009-2019 by the standard population for that year and then multiplying by 100,000. Using background mortality rates, we predicted mortality rates for 2021 using autoregressive integrated moving average models. Further, the expected mortality rates were compared with observed mortality rates. RESULTS: The age-adjusted incidence rate (AIR) of anaphylaxis increased from 4.28 to 22.90 cases per 100,000 population (p = 0.003); myocarditis showed no significant increase, changing from 0.56 to 1.26 cases per 100,000 population (p = 0.276); pericarditis increased from 0.94 to 1.88 cases per 100,000 population (p = 0.005); and GBS increased from 0.78 to 1.21 cases per 100,000 population (p = 0.013). The age-adjusted mortality rate decreased from 645.24 to 475.70 deaths per 100,000 population (p <0.001). The 2021 observed/expected mortality rates for overall (ratio: 1.08, 95% confidence interval [CI]: 1.07-1.08), men (ratio: 1.07, 95% CI: 1.07-1.08), and women (ratio: 1.08, 95% CI: 1.07-1.09), were all significantly higher. When stratified by age group, those aged ≥80 (ratio: 1.16, 95% CI: 1.15-1.17), 60-69 (ratio: 1.11, 95% CI: 1.10-1.13), and 20-29 years old (ratio: 1.07, 95% CI: 1.02-1.13) were also significantly higher. CONCLUSION: Through the estimation of background rates related to anaphylaxis, myocarditis, pericarditis, GBS, and mortality, we established a reference point for evaluating the potential excess occurrence of adverse events following COVID-19 vaccination. This reference point serves as substantive evidence supporting the safety profile of COVID-19 vaccines.

Relationship between perioperative anaphylaxis and history of allergies or allergic diseases: A systematic review and meta-analysis with meta-regression.

STUDY OBJECTIVE: We conducted this meta-analysis to summarize the available evidence and evaluate the relationship between a history of allergies/allergic diseases and perioperative anaphylaxis to offer preventive decision support. DESIGN: Systematic review and meta-analysis of observational studies. SETTING: We searched the MEDLINE (OVID), EMBASE, and the Cochrane Central Register of Controlled Trials databases for observational studies. Two investigators independently performed the search, screened the articles, and collected the study details. MEASUREMENTS: Several databases were systematically searched to evaluate the relationship between a history of allergies/allergic diseases and perioperative anaphylaxis using subgroup analysis, sensitivity analysis and meta-regression. MAIN RESULTS: A total of 19 studies involving 672 anaphylaxis episodes, 5608 immune-mediated reactions, and 1126 severe episodes met the eligibility criteria and were included in this meta-analysis. Drug allergies, food allergies, a history of allergies, and atopy increased the incidence of perioperative anaphylaxis (Drug allergies, odds ratio [OR] 3.54, 95% confidence interval [CI] 1.07-11.69; Food allergies, OR 2.29, 95% CI 1.23-4.26; A history of allergies, OR 4.86, 95% CI 3.65-6.49; Atopy, OR 3.58, 95% CI 1.47-8.71), but not the presence of immune-mediated reactions and the severity of perioperative anaphylaxis. CONCLUSIONS: Patients with previous drug allergies, food allergies, a history of allergies, or atopy are more likely to develop anaphylaxis during the perioperative period. Additional studies should be carried out to determine whether a history of allergies/allergic diseases is a major factor for perioperative anaphylaxis when confounders are controlled.

Peri-operative cardiac arrest due to suspected anaphylaxis as reported to the 7th National Audit Project of the Royal College of Anaesthetists.

The 7th National Audit Project (NAP7) of the Royal College of Anaesthetists studied peri-operative cardiac arrest. Among 59 cases reported as possible anaphylaxis, 33 (56%) were judged to be so by the review panel with high or moderate confidence. Causes in excluded cases included: isolated severe hypotension; bronchospasm; and oesophageal intubation. Severe bronchospasm leading to cardiac arrest was uncommon, but notably in one case led to a reported flat capnograph. In the baseline survey, anaesthetists estimated anaphylaxis as the cause of 10% of cases of peri-operative cardiac arrests and to be among the four most common causes. In a year-long registry of peri-operative cardiac arrest, suspected anaphylaxis was the seventh most common cause accounting for 4% of reports. Initial management was most often with low-dose intravenous adrenaline, and this was without complications. Both the NAP7 baseline survey and case registry provided evidence of reluctance to starting chest compressions when systolic blood pressure had fallen to below 50 mmHg and occasionally even when it was unrecordable. All 33 patients were resuscitated successfully but one patient later died. The one death occurred in a relatively young patient in whom chest compressions were delayed. Overall, peri-operative anaphylaxis leading to cardiac arrest occurred with a similar frequency and patterns of presentation, location, initial rhythm and suspected triggers in NAP7 as in the 6th National Audit Project (NAP6). Outcomes in NAP7 were generally better than for equivalent cases in NAP6.

Anaphylaxis mortality in the perioperative setting: Epidemiology, elicitors, risk factors and knowledge gaps.

Perioperative anaphylaxis (PA) is a severe condition that can be fatal, but data on PA mortality are scarce. The aim of this article is to review the epidemiology, elicitors and risk factors for PA mortality and identify knowledge gaps and areas for improvement regarding the management of severe PA. PA affects about 100 cases per million procedures. Mortality is rare, estimated at 3 to 5 cases per million procedures, but the PA mortality rate is higher than for other anaphylaxis aetiologies, at 1.4% to 4.8%. However, the data are incomplete. Published data mention neuromuscular blocking agents and antibiotics, mainly penicillin and cefazolin, as the main causes of fatal PA. Reported risk factors for fatal PA vary in different countries. Most frequently occurring comorbidities are obesity, male gender, cardiovascular diseases and ongoing treatment with beta-blockers. However, there are no clues about how these factors interact and the impact of individual risk factors. The pathophysiology of fatal PA is still not completely known. Genetic factors such as deficiency in PAF-acetyl hydrolase and hereditary alpha-tryptasemia, have been reported as modulators of severe anaphylaxis and possible targets for specific treatments. Our review underlines unmet needs in the field of fatal PA. Although we confirmed the need for timely administration of an adequate dose of adrenaline and the proper infusion of fluids, there is no evidence-based data on the proper dose of intravenous titrated adrenaline and which clinical manifestations would flag the need for fluid therapy. There are no large clinical studies supporting the administration of alternative vasopressors, such as glucagon and methylene blue. Further research on pathophysiological mechanisms of PA and its severity may address these issues and help clinicians to define new therapeutic approaches.

Examining cefazolin utilization and perioperative anaphylaxis in patients with and without a penicillin allergy label: A cross-sectional study.

STUDY OBJECTIVE: To compare the occurrence of cefazolin perioperative anaphylaxis (POA) in patients with and without a penicillin allergy label (PAL) to determine whether the prevalence of cefazolin POA differs based on the presence of a PAL. DESIGN: Cross-sectional study. SETTING: A large U.S. healthcare system in the Baltimore-D.C. region, July 2017 to July 2020. PATIENTS: 112,817 surgical encounters across inpatient and outpatient settings in various specialties, involving 90,089 patients. Of these, 4876 (4.3%) encounters had a PAL. INTERVENTIONS: Perioperative cefazolin administration within 4 h before surgery to 4 h after the procedure began. MEASUREMENTS: The primary outcome was cefazolin POA in patients with and without PALs. Potential POA cases were identified based on tryptase orders or diphenhydramine administrations within the initial cefazolin administration to 6 h postoperatively. Verification included two validation steps. The first checked for hypersensitivity reaction (HSR) documentation, and the second, led by Allergy specialists, identified POA and the probable culprit. The secondary outcome looked at cefazolin use trends in patients with a PAL, stratified by setting and specialty. MAIN RESULTS: Of 112,817 encounters, 1421 (1.3%) had possible cefazolin HSRs. Of these, 22 (1.5%) had POA, resulting in a 0.02% prevalence. Of these, 13 (59.1%) were linked to cefazolin and 9 (40.9%) attributed to other drugs. Only one cefazolin POA case had a PAL, indicating no significant difference in cefazolin POA prevalence between patients with and without PALs (p = 0.437). Perioperative cefazolin use in patients with PALs steadily increased from 2.6% to 6.0% between 2017 and 2020, specifically in academic settings. CONCLUSIONS: The prevalence of cefazolin POA does not exhibit significant differences between patients with and without PALs, and notably, the incidence remains remarkably low. Based on these findings, it is advisable to view cefazolin as an acceptable choice for prophylaxis in patients carrying a PAL.

Infant Whole-Cell Versus Acellular Pertussis Vaccination in 1997 to 1999 and Risk of Childhood Hospitalization for Food-Induced Anaphylaxis: Linked Administrative Databases Cohort Study.

BACKGROUND: Evidence suggests that children who had received an initial priming dose of whole-cell pertussis (wP) vaccine, rather than acellular pertussis (aP) vaccine, had a lower risk of developing IgE-mediated food allergy, the most common cause of anaphylaxis-related hospital presentations of childhood. OBJECTIVE: To assess the association between wP versus aP vaccination in infancy and subsequent hospital presentations for anaphylaxis. METHODS: This study was preregistered under PMID 34874968. Perinatal records for a cohort of New South Wales-born children (1997-1999) receiving their first dose of pertussis-containing vaccine before age 4 months were probabilistically linked to hospital and immunization records. We used adjusted Cox models to estimate hazard ratios (aHRs) and 95% CIs for anaphylaxis-coded hospitalizations. RESULTS: There were 218,093 New South Wales-born children who received a first dose of wP or aP before age 4 months. Among these children, 86 experienced at least one hospitalization for food-induced anaphylaxis at age 5-15 years (range of events per patient, one to three). The person-time of follow-up was 1,476,969 years, and 665,519 years for children vaccinated with wP as a first dose (wP-1 children) and aP as a first dose (aP-1 children), respectively. The incidence rates for first hospitalization for food anaphylaxis were 3.5 (95% CI, 2.6-4.6) and 5.1 (95% CI, 3.5-7.1) per 100,000 child-years among wP-1 children and aP-1 children, respectively (aHR for wP vs aP = 0.47; 95% CI, 0.26-0.83). For first admission for venom anaphylaxis, the incidence rate was 4.9 (95% CI, 3.9-6.2) per 100,000 child-years among wP-1 children and 5.1 (95% CI, 3.5-7.1) per 100,000 child-years among aP-1 children (aHR for wP vs aP = 0.92; 95% CI, 0.53-1.60), and for all-cause anaphylaxis, the incidence rate was 10.6 (95% CI, 9.0-12.4) per 100,000 child-years among wP-1 children and 12.8 (95% CI, 10.2-15.8) per 100,000 child-years among aP-1 children (aHR for wP vs aP = 0.92; 95% CI, 0.53-1.60). CONCLUSION: Vaccination with wP in infancy was associated with a lower risk of hospitalizations for food-induced anaphylaxis (and therefore severe IgE-mediated food allergy) occurring in childhood.

Evaluation of the Regulatory Required Post-Authorization Safety Study for Propacetamol: Nested Case-Control and Case-Time-Control Studies.

PURPOSE: Following the withdrawal of propacetamol in Europe owing to safety issues, the regulatory authority of South Korea requested a post-marketing surveillance study to investigate its safety profile. MATERIALS AND METHODS: We conducted nested case-control and case-time-control (CTC) analyses of cases and controls identified for outcomes of interest, including anaphylaxis, thrombosis, and Stevens-Johnson syndrome (SJS), using the claims database of South Korea, 2010-2019. Risk-set sampling was used to match each case with up to 10 controls for age, sex, cohort entry date, and follow-up duration. Exposure to anaphylaxis, thrombosis, and SJS was assessed within 7, 90, and 30 days of the index date, respectively. We calculated odds ratios (OR) with 95% confidence intervals (CIs) using conditional logistic regression to assess the risk of outcomes associated with propacetamol. RESULTS: We identified cases of anaphylaxis (n=61), thrombosis (n=95), and SJS (n=1) and matched them to controls (173, 268, and 4, respectively). In the nested case-control analysis, the ORs for anaphylaxis and SJS were inestimable given the small number of propacetamol users during the risk period; meanwhile, the OR for thrombosis was 1.60 (95% CI 0.71-3.62). In the CTC design, the effect estimate was only estimated for thrombosis (OR 0.56, 95% CI 0.09-3.47). CONCLUSION: In both nested case-control and CTC analyses, propacetamol was not associated with an increased risk of anaphylaxis, thrombosis, or SJS. The findings from this study, which used routinely collected clinical data, provide reassuring real-world evidence regarding the safety of propacetamol in a nationwide population to support regulatory decision-making.

The role of skin tests with polyethylene glycol and polysorbate 80 in the vaccination campaign for COVID-19: results from an Italian multicenter survey.

Summary: Background. International guidelines suggested skin tests with Polyethylene-glycol (PEG) and polysorbate 80 (PS-80), to investigate a possible hypersensitivity to these excipients either to identify subjects at risk of developing allergic reactions to Covid-19 vaccines, or in patients with suspected IgE mediated hypersensitivity reactions (HR) to the Covid-19 vaccine. The main purpose of this study was to investigate the prevalence of PEG and PS sensitization in patients with a clinical history of HR to drugs containing PEG/PS and in patients with a suspected Covid-19 vaccine immediate HR. Methods. This was a multicenter retrospective study conducted by allergists belonging to 20 Italian medical centers. Skin testing was performed in 531 patients with either a clinical history of suspected hypersensitivity reaction (HR) to drugs containing PEG and/or PS-80 (group 1:362 patient) or a suspected HR to Covid-19 vaccines (group 2: 169 patient), as suggested by the AAIITO/SIAAIC guidelines for the "management of patients at risk of allergic reactions to Covid-19 vaccines" [1]. Results. 10/362 (0.02%) had positive skin test to one or both excipients in group 1, 12/169 (7.1%) in group 2 (p less than 0.01). In group 2 HRs to Covid-19 vaccines were immediate in 10/12 of cases and anaphylaxis occurred in 4/12 of patients. Conclusions. The positivity of skin test with PEG and or PS before vaccination is extremely rare and mostly replaceable by an accurate clinical history. Sensitization to PEG and PS has to be investigated in patients with a previous immediate HR to a Covid-19 vaccine, in particular in patients with anaphylaxis.

Incidence of anaphylaxis to YF-VAX® yellow fever vaccination: a retrospective evaluation of vaccine adverse event reports 1999-2018.

BACKGROUND: The incidence of anaphylaxis after receipt of yellow fever (YF) vaccine is highly variable based upon previously published reports. Anaphylaxis after receiving the YF vaccine has been reported to range from 0 up to 22 per 1 000 000 doses. Our clinical experience suggested increased incidence, which prompted our investigation. We sought to evaluate the current incidence rate of anaphylaxis after receipt of the 17D-204 strain YF-VAX® brand reported in the US. METHODS: We performed a retrospective review of the Vaccine Adverse Event Reporting System (VAERS) reports of anaphylaxis after receiving the YF-VAX vaccine occurring between 1 October 1999 and 30 September 2018. We utilized the Brighton Collaboration Case Definition and inclusion determination was made by a board-certified allergist. We also obtained the total number of YF-VAX doses distributed across the US during this same time-period and then calculated an updated incidence rate of YF-VAX vaccine-associated anaphylaxis. RESULTS: We identified 132 potential cases of possible or probable anaphylaxis. Of these, 111 met inclusion criteria: level 1 (n = 51), level 2 (n = 59) and level 3 (n = 1). The manufacturer reported a total distribution of 7 624 160 doses of YF-VAX from 1 October 1999 to 30 September 2018. The calculated incidence rate of YF-VAX vaccine-associated anaphylaxis is estimated at 14.6 events per 1 000 000 doses. CONCLUSIONS: We conclude the estimated rate of anaphylaxis per VAERS reports is 14.6 events per 1 000 000 doses after YF-VAX vaccination. This is consistent with some previous reports and substantially higher than rates of anaphylaxis after other vaccines.

Real-Life Adherence to Venom Immunotherapy and Adrenaline Autoinjector.

INTRODUCTION: Venom immunotherapy (VIT) and adrenaline autoinjector (AAI) are important therapies in venom anaphylaxis. Adherence to VIT and AAI in patients with venom allergy has been evaluated in a few studies; however, solid data are lacking. This study aimed to evaluate VIT and AAI retrieval rates in patients with venom allergy with a special focus on adherence to treatment. Adherence was compared to subcutaneous immunotherapy (SCIT) with inhalant allergens. METHODS: This was a retrospective study among patients registered for allergen immunotherapy at the Allergy Center, Odense University Hospital, Denmark, from January 1, 2010, to December 31, 2014. Data on purchased immunotherapy and AAI were obtained from the Danish National Health Service Prescription Database. Multivariable logistic regression was used to analyze if allergen, age, sex, mastocytosis, and treatment site affected adherence. RESULTS: The 3-year adherence to VIT was 92.4% (244/264) compared to 87.4% (215/246) in SCIT with inhalant allergens, and the 5-year adherence to VIT was 84.1% (222/264) compared to 74.8% (184/246) in SCIT with inhalant allergens (p = 0.045). Females treated with VIT were more adherent than males (p = 0.45 [3-year], p = 0.008 [5-year]), whereas allergen, age, mastocytosis, or treatment site did not significantly affect adherence. Only 28.6% of patients (12/42) purchased an AAI after premature termination of VIT. CONCLUSION: In this register-based study, we found that the 3- and 5-year adherences to VIT and SCIT with inhalant allergens are at the upper end of the spectrum hitherto reported. Patients' 5-year adherence to VIT was higher than patients' 5-year adherence to SCIT with inhalant allergens. If VIT was prematurely terminated, less than 1/3 would have purchased an AAI.

Perioperative hypersensitivity in children: A prospective multidisciplinary study.

BACKGROUND: There are few studies of perioperative hypersensitivity reactions in children. The diagnosis of perioperative hypersensitivity reactions may be under estimated because it is difficult to recognize the reactions. Anaphylaxis may go unnoticed because of patient unconsciousness. Urticaria may be missed due to sterile drapes. The aim of this study was to prospectively evaluate perioperative hypersensitivity reactions. METHODS: In this prospective study, patients with suspected perioperative hypersensitivity reactions aged 0-18 years who underwent surgery at the Department of Pediatric Surgery, Cerrahpasa Faculty of Medicine, between 2019 and 2021 were investigated. Suspected reactions in the perioperative period were graded according to the Ring and Messmer scale. Patients with suspected reactions were examined 4-6 weeks after the reaction. If necessary, specific IgE and basophil activation tests were performed. Reactions of grades III-IV were considered anaphylaxis. If one test modality was strongly positive and there was a relevant time point or repeated allergic reactions, or at least two test modalities were positive, hypersensitivity was confirmed. In all patients, serum tryptase levels were analyzed at the time of the reaction, 2 h after the reaction, and 4-6 weeks after the reaction as part of the allergic evaluation. RESULTS: A total of 29 patients (8 female, 21 male) suspected of having an intraoperative reaction during the study were included in the analysis. Perioperative hypersensitivity reactions were noted in 1 patient. The incidence of perioperative hypersensitivity reactions was reported to be 0.03% (n = 1/2861). While anaphylaxis was confirmed in 1 patient, 5 patients were considered possible anaphylaxis cases. CONCLUSION: Perioperative hypersensitivity reactions can be life-threatening and may recur with further administration. Collaboration between pediatric surgeons, anesthesiologists, and allergists can prevent further reactions. All suspected cases should be evaluated by an experienced allergist soon after the initial reaction.

Adrenaline autoinjectors for Australian out-of-hospital anaphylaxis: where to from here?

Intramuscular adrenaline autoinjectors are accepted as first-line treatment for out-of-hospital anaphylaxis but face ongoing issues of patient nonadherence related to drug expiry, availability, correct administration, and public recognition of the disease. Adrenaline is associated with possible harms in patients with defined comorbidities but is still considered preferable. Further research and policy is required to facilitate the effective treatment of anaphylaxis.

Factors Associated With Epinephrine Use in the Treatment of Anaphylaxis in Infants and Toddlers.

BACKGROUND: Undertreatment of anaphylaxis with epinephrine continues to be an unmet need and is a particular challenge among infants and toddlers. OBJECTIVE: To address this gap by identifying barriers and solutions to appropriate and timely administration of epinephrine. METHODS: We conducted a national online survey among primary caregivers of children who experienced a severe food-induced allergic reaction when younger than 36 months. Outcomes of interest included epinephrine use in community and health care settings to treat probable anaphylaxis. RESULTS: Of 264 probable anaphylaxis cases, 39% of infants (aged <12 months) and 61% of toddlers (aged 12-35 months) received epinephrine at any time during the child's most severe allergic reaction (P = .001). A previous diagnosis of a food allergy was reported in 62% of cases where epinephrine was used compared with 26% of cases where epinephrine was not used (P < .001). In children with a previous diagnosis of a food allergy, epinephrine was used in 89% of those who were prescribed an anaphylaxis action plan compared with 50% of those without a plan (P = .001). The adjusted odds ratio for the association between having an anaphylaxis action plan and epinephrine use in cases of probable anaphylaxis was 5.39 (95% confidence interval, 2.18-13.30). CONCLUSIONS: Epinephrine use at any time (including in health care settings) during probable anaphylaxis is more likely in infants and toddlers with a previously diagnosed food allergy than those without diagnosis. The provision of an anaphylaxis action plan is also associated with increased epinephrine use during probable anaphylaxis in this population.

Variation in the Guidelines for the Acute Management of Anaphylaxis in Pediatric Patients: An International Narrative Review.

OBJECTIVES: Evidence-based guidelines have been created and disseminated by multiple organizations to standardize the care of pediatric patients with anaphylaxis. Differences across these guidelines can cause confusion and potentially errors in clinical practice leading to patient harm. The aim of this study was to describe and identify patterns of variation in the current guidelines. METHODS: A narrative review with 3 major components was designed. First, a narrative review of current, peer-reviewed, guidelines published by national and international allergy and immunology, pediatric, and emergency medicine organizations was performed. That was followed by a gray literature review of guidelines by resuscitation councils and national health organizations. The third component focused on the translation of these guidelines at local and institutional levels by reviewing clinical pathways published by academic institutions. RESULTS: With regard to the fixed epinephrine autoinjector dosing, 50% (6 of 12) of the reviewed guidelines offered weight-based and 41.7% (5 of 12) age-based dosing recommendations. Furthermore, different weight cutoffs for the 0.15- and 0.3-mg autoinjectors were identified among guidelines. Variation was identified in the description of intramuscular epinephrine concentration ("1:1000," "1 mg/mL," or both), the recommended concentration for intravenous administration ("1:10,000" or "1:1000"), or the rate of infusion or titration. Eight of the 12 guidelines (66.7%) recommend a dose in milligrams, and 33.3% (4 of 12) in micrograms. Five of 12 (41.7%) used both milliliters and milligrams or micrograms. CONCLUSIONS: Notable variation in the current guidelines for the acute management of anaphylaxis in the pediatric population was identified. Flagging this variability could help inform a consensus-based approach toward harmonization of guidelines, which in turn could streamline the management of anaphylaxis in pediatric patients across the United States, Canada, Ireland, the United Kingdom, Europe, Australia, and New Zealand, and hopefully prevent errors and mitigate patient harm.

Predictors of severe and recurrent adult anaphylaxis, and gaps in the cascade of care: a retrospective, single-centre study 2009-2018.

BACKGROUND: Anaphylaxis is a severe, potentially fatal, systemic allergic reaction. Understanding predictors of recurrent and severe anaphylaxis in adults, and identifying gaps in ongoing anaphylaxis care, is needed to minimise its impact. AIMS: To evaluate the risk factors in adults with severe and recurrent anaphylaxis presentations and to evaluate the management of patients in regard to the recommended cascade of care. METHODS: We completed a retrospective audit of adults with confirmed anaphylaxis who presented to an inner-city emergency department from 1 January 2009 through 31 December 2018. Data recorded included demographics, background history, medication use, severity, co-factors, triggers, management, discharge disposition and referral for follow-up. Data were managed in REDCap and analysed using Stata. Associations were assessed through odds ratios (ORs) and t tests. RESULTS: Six hundred sixteen individuals had 689 episodes of anaphylaxis over the audit period. Age over 65 (OR: 5.4 (95% confidence interval, CI: 2.3-13.2), P < 0.0001) and history of asthma (OR: 1.6 (95% CI: 1.03-2.5), P = 0.03) were independent risk factors for severe anaphylaxis. History of food allergy (P < 0.001) and food as the trigger were associated with recurrent presentations (OR: 2.1, 95% CI: 1.1-3.9, P = 0.01). Only 19% of patients met the recommended cascade of care, with post-adrenaline monitoring and recommending follow-up with an allergy specialist demonstrating the largest gaps. There were increased presentations with time but no difference in triggers or severity. CONCLUSIONS: Increased age and asthma were identified as risk factors for severe presentations. History of food allergy was a risk factor for recurrent presentations. Further research is needed on the gaps in care for adults with anaphylaxis to identify the reasons why, so we can better care for these patients.

Clinical impact of the TPSAB1 genotype in mast cell diseases: A REMA study in a cohort of 959 individuals.

BACKGROUND: A close association between hereditary alpha-tryptasemia (HAT) and mast cell (MC) disorders has been previously reported. However, the relationship between HAT and the diagnostic subtypes and clinical features of MC disorders still remains to be established. OBJECTIVE: To determine the prevalence of HAT in healthy donors (HD) vs patients with different diagnostic subtypes of MC activation syndromes (MCAS) and mastocytosis, and its relationship with the clinical behavior of the disease. METHODS: A total of 959 subjects were studied including 346 healthy donors (HD), 464 mastocytosis, and 149 non-clonal MCAS patients. Molecular studies to assess the TPSAB1 genotype were performed, and data on serum baseline tryptase (sBT) and basal MC-mediator release episodes and triggers of anaphylaxis were collected. RESULTS: HAT was detected in 15/346 (4%) HD versus 43/149 (29%) non-clonal MCAS and 84/464 (18%) mastocytosis cases. Among mastocytosis, HAT was more frequently found in patients with MC-restricted KITD816V (21% vs. 10% among multilineage KITD816V patients; p = .008). Overall, median sBT was higher in cases presenting with HAT (28.9 vs. 24.5 ng/mL; p = .008), while no significant differences in sBT were observed among HAT+ mastocytosis patients depending on the presence of 1 vs. ≥2 extra copies of the α-tryptase gene (44.1 vs. 35.2 ng/mL, p > .05). In turn, anaphylaxis was more frequently observed in HAT+ versus HAT- mastocytosis patients (76% vs. 65%; p = .018), while HAT+ and HAT- patients who did not refer anaphylaxis as the presenting symptom (n = 308) showed a similar prevalence of subsequent anaphylaxis (35% vs. 36%, respectively). CONCLUSION: The frequency of HAT in MC disorders varies according to the diagnostic subtype of the disease. HAT does not imply a higher risk (and severity) of anaphylaxis in mastocytosis patients in whom anaphylaxis is not part of the presenting symptoms of the disease.

A case-control study for comorbidity and laboratory factors associated with food-induced anaphylaxis.

Background: Food-induced anaphylaxis (FIA) is a serious and potentially life-threatening allergic reaction triggered by food allergens. Objective: This case-control study aimed to investigate comorbidities and laboratory factors associated with FIA in the pediatric population of Israel. Methods: Retrospective data from the electronic health records of Leumit Health Care Services were used to identify 711 pediatric patients with FIA and 2560 subjects with food allergy and without anaphylaxis matched for age, gender, and ethnicity. Comorbidities were identified based on medical billing diagnosis codes, and laboratory characteristics were compared between the two groups. Results: The mean ± standard deviation age of patients with FIA was 4.1 ± 4.1 years, and 37.3% were girls. Laboratory analysis revealed increased eosinophil counts (p < 0.001), elevated immunoglobulin E (IgE) (p < 0.001), and IgA levels (p = 0.001) in the FIA group compared with the controls. With regard to comorbidities, the FIA group had higher prevalence rates of allergic diseases, including allergic rhinitis (odds ratio [OR] 1.72; p < 0.001), allergic conjunctivitis (OR 1.84; p = 0.001), asthma (OR 1.36; p < 0.001), angioedema (OR 6.37; p < 0.001), atopic dermatitis (OR 1.77; p < 0.001), and contact dermatitis (OR 1.42; p = 0.001). There was a trend toward significance for chronic spontaneous urticaria (p = 0.051). There was a significant negative association between helminthiases, particularly enterobiasis, and FIA (OR 0.76 [95% confidence interval, 0.59-0.98]; p = 0.029). Conclusion: This study provides valuable epidemiologic evidence on the associations among FIA, comorbidities, and laboratory factors in the pediatric population.