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Anaphylaxis Articles

J Allergy Clin Immunol. 2016 Apr;137(4):1128-37.e1. doi: 10.1016/j.jaci.2015.11.015. Epub 2016 Jan 21.
Anaphylaxis in children and adolescents: The European Anaphylaxis Registry.
Grabenhenrich LB, Dölle S, Moneret-Vautrin A, Köhli A, Lange L, Spindler T, Ruëff F, Nemat K, Maris I, Roumpedaki E, Scherer K, Ott H, Reese T, Mustakov T, Lang R, Fernandez-Rivas M, Kowalski ML, Bilò MB, Hourihane JO, Papadopoulos NG, Beyer K, Muraro A, Worm M.

Abstract

BACKGROUND:

Anaphylaxis in children and adolescents is a potentially life-threatening condition. Its heterogeneous clinical presentation and sudden occurrence in virtually any setting without warning have impeded a comprehensive description.

OBJECTIVE:

We sought to characterize severe allergic reactions in terms of elicitors, symptoms, emergency treatment, and long-term management in European children and adolescents.

METHODS:

The European Anaphylaxis Registry recorded details of anaphylaxis after referral for in-depth diagnosis and counseling to 1 of 90 tertiary allergy centers in 10 European countries, aiming to oversample the most severe reactions. Data were retrieved from medical records by using a multilanguage online form.

RESULTS:

Between July 2007 and March 2015, anaphylaxis was identified in 1970 patients younger than 18 years. Most incidents occurred in private homes (46%) and outdoors (19%). One third of the patients had experienced anaphylaxis previously. Food items were the most frequent trigger (66%), followed by insect venom (19%). Cow's milk and hen's egg were prevalent elicitors in the first 2 years, hazelnut and cashew in preschool-aged children, and peanut at all ages. There was a continuous shift from food- to insect venom- and drug-induced anaphylaxis up to age 10 years, and there were few changes thereafter. Vomiting and cough were prevalent symptoms in the first decade of life, and subjective symptoms (nausea, throat tightness, and dizziness) were prevalent later in life. Thirty percent of cases were lay treated, of which 10% were treated with an epinephrine autoinjector. The fraction of intramuscular epinephrine in professional emergency treatment increased from 12% in 2011 to 25% in 2014. Twenty-six (1.3%) patients were either admitted to the intensive care unit or had grade IV/fatal reactions.

CONCLUSIONS:

The European Anaphylaxis Registry confirmed food as the major elicitor of anaphylaxis in children, specifically hen's egg, cow's milk, and nuts. Reactions to insect venom were seen more in young adulthood. Intensive care unit admissions and grade IV/fatal reactions were rare. The registry will serve as a systematic foundation for a continuous description of this multiform condition.

SUMMARY:

The authors proposed the analysis of children and adolescents data collected from July 2007 to March 2015 in the European Anaphylaxis Registry. Data collected from 10 European countries confirmed that foods are the main triggers of anaphylaxis in children and insect venom in young adults. Most of episodes occurred in private homes. Although one third presented history of previous reactions, grade IV and fatal reactions were rare.

Allergy. 2017 Jan;72(1):120-125. doi: 10.1111/all.13006. Epub 2016 Sep 1.
Decreasing the undernotification of anaphylaxis deaths in Brazil through the International Classification of Diseases (ICD)-11 revision.
Tanno LK, Bierrenbach AL, Calderon MA, Sheikh A, Simons FE, Demoly P; Joint Allergy Academies.

Abstract

BACKGROUND:

In 2012, an analysis of the Brazilian mortality database demonstrated undernotification of anaphylaxis deaths due, at least in part, to difficult coding under the International Classification of Diseases (ICD)-10. This work triggered a cascade of strategic international actions supported by the Joint Allergy Academies and the ICD World Health Organization (WHO) representatives to update the classifications of allergic disorders for the ICD-11 revision. These efforts have resulted in the construction of the new 'Allergic and hypersensitivity conditions' section under the 'Disorders of the Immune system' chapter.

OBJECTIVE:

To analyze the capacity of the new ICD-11 revision to capture anaphylaxis deaths.

METHODS:

We re-estimated the anaphylaxis deaths that occurred in Brazil during the period 2008 to 2010, utilizing this new framework and the database of the Brazilian mortality information system that had initially been extracted in May 2011. However, in 2016, a manual review of each of the 3638 records was performed.

RESULTS:

We identified 639 anaphylaxis deaths, of which 95% were classified as 'definitive anaphylaxis deaths'. In contrast to the 2012 published data, we found a higher number of cases; moreover, all 606 definitive anaphylaxis deaths would be considered as underlying causes of death utilizing the ICD-11 revision.

CONCLUSION:

This study is the first example of how the new 'Allergic and hypersensitivity conditions' section of the forthcoming ICD-11 can improve the quality of official vital statistics data and the visibility of an important public health concern. This research will facilitate comprehensive, comparable population-based epidemiologic data collection on anaphylaxis.

SUMMARY:

The authors proposed reviewing the data published in 2012, in which it has been demonstrated the undernotification of anaphylaxis deaths due to difficult coding under the World Health Organization (WHO) International Classification of Diseases (ICD)-10. Clearer was the effect on the accuracy reaching 95% for definite anaphylaxis when ICD11 was used. This re-analysis of Brazilian data applying the pioneer ICD-11 framework proved its usability and feasibility on improving quality of official vital statistics data.

J Allergy Clin Immunol. 2016 Mar;137(3):868-78. doi: 10.1016/j.jaci.2015.07.048. Epub 2015 Oct 6.
Risk of anaphylaxis after vaccination in children and adults.
McNeil MM, Weintraub ES, Duffy J, Sukumaran L, Jacobsen SJ, Klein NP, Hambidge SJ, Lee GM, Jackson LA, Irving SA, King JP, Kharbanda EO, Bednarczyk RA, DeStefano F.

Abstract

BACKGROUND:

Anaphylaxis is a potentially life-threatening allergic reaction. The risk of anaphylaxis after vaccination has not been well described in adults or with newer vaccines in children.

OBJECTIVE:

We sought to estimate the incidence of anaphylaxis after vaccines and describe the demographic and clinical characteristics of confirmed cases of anaphylaxis.

METHODS:

Using health care data from the Vaccine Safety Datalink, we determined rates of anaphylaxis after vaccination in children and adults. We first identified all patients with a vaccination record from January 2009 through December 2011 and used diagnostic and procedure codes to identify potential anaphylaxis cases. Medical records of potential cases were reviewed. Confirmed cases met the Brighton Collaboration definition for anaphylaxis and had to be determined to be vaccine triggered. We calculated the incidence of anaphylaxis after all vaccines combined and for selected individual vaccines.

RESULTS:

We identified 33 confirmed vaccine-triggered anaphylaxis cases that occurred after 25,173,965 vaccine doses. The rate of anaphylaxis was 1.31 (95% CI, 0.90-1.84) per million vaccine doses. The incidence did not vary significantly by age, and there was a nonsignificant female predominance. Vaccine-specific rates included 1.35 (95% CI, 0.65-2.47) per million doses for inactivated trivalent influenza vaccine (10 cases, 7,434,628 doses given alone) and 1.83 (95% CI, 0.22-6.63) per million doses for inactivated monovalent influenza vaccine (2 cases, 1,090,279 doses given alone). The onset of symptoms among cases was within 30 minutes (8 cases), 30 to less than 120 minutes (8 cases), 2 to less than 4 hours (10 cases), 4 to 8 hours (2 cases), the next day (1 case), and not documented (4 cases).

CONCLUSION:

Anaphylaxis after vaccination is rare in all age groups. Despite its rarity, anaphylaxis is a potentially life-threatening medical emergency that vaccine providers need to be prepared to treat.

SUMMARY:

The authors proposed identify the incidence of vaccine-induced anaphylaxis in children and adults. After collecting data from US medical registries from January 2009 to December 2011 and validated by the Brighton Collaboration criteria, 33 cases of 25,173,965 vaccine doses have been identified. Although the rate of anaphylaxis was 1.3 per million vaccine doses, life- threatening cases have been identified.

Allergy. 2016 Nov 22. doi: 10.1111/all.13093. [Epub ahead of print]
Field-testing the new anaphylaxis' classification for the WHO International Classification of Diseases-11 revision.
Tanno LK, Molinari N, Bruel S, Bourrain JL, Calderon MA, Aubas P, Demoly P; Joint Allergy Academies.

Abstract

BACKGROUND:

To consolidate the new classification model addressed to the allergic and hypersensitivity conditions according to the International Classification of Diseases (ICD)-11 revision timeline, we here propose real-life application of quality assurance methodology to evaluate sensitivity and accuracy of the 'Anaphylaxis' subsection.

METHODS:

We applied field-testing methodology by analysing all the consecutive inpatients' files documented as allergies from the University Hospital of Montpellier electronic database for the period of 1 year. The files clinically validated as being anaphylaxis were manually blind-coded under ICD-10 and current ICD-11 beta draft. The correspondence of coding and the impressions regarding sensibility were evaluated.

RESULTS:

From all 2318 files related to allergic or hypersensitivity conditions, 673 had some of the anaphylaxis ICD-10 codes; 309 files (46%) from 209 patients had anaphylaxis and allergic or hypersensitivity comorbidities description. The correspondence between the two coders was perfect for 162 codes from all 309 entities (52.4%) (Cohen-kappa value 0.63) with the ICD-10 and for 221 codes (71.5%) (Cohen-kappa value 0.77) with the ICD-11. There was a high agreement regarding sensibility of the ICD-11 usability (Cohen-kappa value 0.75).

CONCLUSION:

We here propose the first attempt of real-life application to validate the new ICD-11 'Anaphylaxis' subsection. Clearer was the improvement in accuracy reaching 71.5% of agreement when ICD-11 was used. By allowing all the relevant diagnostic terms for anaphylaxis to be included into the ICD-11 framework, WHO has recognized their importance not only to clinicians but also to epidemiologists, statisticians, healthcare planners and other stakeholders.

SUMMARY:

This study is the first attempt of a real-life application to validate the new International Classification of Diseases (ICD)-11 Anaphylaxis subsection. After evaluating 2318 hospitalization files recorded in the University Hospital of Montpellier for one-year period, 209 have been identified as anaphylaxis by clinical and blinded-coding validations. The methodology applied has been extensively discussed with the World Health Organization (WHO) ICD-11 revision governance and reached improvement in accuracy 71.5% of agreement when ICD-11 was used.

J Allergy Clin Immunol Pract. 2015 Jan-Feb;3(1):76-80. doi: 10.1016/j.jaip.2014.06.007. Epub 2014 Aug 29.
Epinephrine in anaphylaxis: higher risk of cardiovascular complications and overdose after administration of intravenous bolus epinephrine compared with intramuscular epinephrine.
Campbell RL, Bellolio MF, Knutson BD, Bellamkonda VR, Fedko MG, Nestler DM, Hess EP.

Abstract

BACKGROUND:

Epinephrine is the drug of choice for the management of anaphylaxis, and fatal anaphylaxis is associated with delayed epinephrine administration. Data on adverse cardiovascular (CV) complications and epinephrine overdose are limited.

OBJECTIVE:

To compare rates of CV adverse events and epinephrine overdoses associated with anaphylaxis management between various routes of epinephrine administration among patients with anaphylaxis in the emergency department.

METHODS:

This was an observational cohort study from April 2008 to July 2012. Patients in the emergency department who met diagnostic criteria for anaphylaxis were included. We collected demographics; route of epinephrine administration; trigger; overdose; and adverse CV events, including arrhythmia, cardiac ischemia, stroke, angina, and hypertension.

RESULTS:

The study cohort included 573 patients, of whom, 301 (57.6%) received at least 1 dose of epinephrine. A total of 362 doses of epinephrine were administered to 301 patients: 67.7% intramuscular (IM) autoinjector, 19.6% IM injection, 8.3% subcutaneous injection, 3.3% intravenous (IV) bolus, and 1.1% IV continuous infusion. There were 8 CV adverse events and 4 overdoses with 8 different patients. All the overdoses occurred when epinephrine was administered IV bolus. Adverse CV events were associated with 3 of 30 doses of IV bolus epinephrine compared with 4 of 316 doses of IM epinephrine (10% vs 1.3%; odds ratio 8.7 [95% CI, 1.8-40.7], P = .006). Similarly, overdose occurred with 4 of 30 doses of IV bolus epinephrine compared with 0 of 316 doses of IM epinephrine (13.3% vs 0%; odds ratio 61.3 [95% CI, 7.5 to infinity], P < .001).

CONCLUSION:

The risk of overdose and adverse CV events is significantly higher with IV bolus epinephrine administration. Analysis of the data supports the safety of IM epinephrine and a need for extreme caution and further education about IV bolus epinephrine in anaphylaxis.

SUMMARY:

The authors propose a cohort study from April 2008 to July 2012 to compare rates of cardiovascular adverse events and epinephrine overdoses associated with anaphylaxis management between various routes of epinephrine administration among patients with anaphylaxis in the emergency department. The results support the safety of IM epinephrine and a need for extreme caution and further education about IV bolus epinephrine in anaphylaxis.

Acad Emerg Med. 2016 Dec 15. doi: 10.1111/acem.13147. [Epub ahead of print]
H1-antihistamines reduce progression to anaphylaxis among emergency department patients with allergic reactions.
Kawano T, Scheuermeyer FX, Gibo K, Stenstrom R, Rowe B, Grafstein E, Grunau B.

Abstract

OBJECTIVES:

H1-antihistamines (H1a) can be used to treat ED patients with allergic reactions; however, this is inconsistently done, likely as there is no evidence that this therapy has an impact on serious outcomes. Among emergency department (ED) patients initially presenting with allergic reactions, we investigated whether H1a were associated with lower rates of progression to anaphylaxis.

METHODS:

This was a retrospective cohort study conducted at two urban Canadian EDs from April 1, 2007 to March 31, 2012. We included consecutive adult patients with allergic reactions while excluding those presenting with anaphylaxis, according to pre-specified criteria. The primary outcome was the proportion of patients who subsequently developed anaphylaxis during medical care, either by emergency medical services (EMS) or in the ED. A pre-specified subgroup analysis excluded patients who received H1a prior to EMS or ED contact. We compared those who received H1a and those who did not, and used multivariable regression and propensity score adjustment techniques to compare outcomes.

RESULTS:

Of 2,376 overall patients included, 1,880 (79.1%) were managed with H1a. Of the latter group, 36 / 1,880 (1.9%) developed anaphylaxis, compared to 17 / 496 (3.4%) in the non-H1a-treated group (adjusted odds ratio [AOR] 0.34, 95% CI 0.17 to 0.70; number needed to treat [NNT] to benefit 44.74, 95% CI 35.36 to 99.67). In the subgroup analysis of 1,717 patients who did not receive H1a prior to EMS or ED contact, a similar association was observed (AOR 0.26, 95% CI 0.10 to 0.50; NNT to benefit 38.20, 95% CI 32.58 to 55.24).

CONCLUSIONS:

Among ED patient with allergic reactions, H1a administration was associated with a lower likelihood of progression to anaphylaxis. These data indicate that early H1a treatment in the ED or prehospital setting may decrease progression to anaphylaxis. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

KEYWORDS: Allergic reactions; Anaphylaxis; emergency department; prevention
PMID: 27976492
DOI: 10.1111/acem.13147

SUMMARY:

This study is interesting, despite being retrospective in design. It gives a signal on the potential preventive effect of antihistamines in reducing the progression from mild allergic reactions to anaphylaxis. It would need validation in prospective studies, and it is clear that it does not refer to treatment of established anaphylaxis with antihistamines.

Curr Opin Allergy Clin Immunol. 2016 Jun;16(3):244-9. doi: 10.1097/ACI.0000000000000261.
Component-resolved diagnosis in anaphylaxis.
Cardona V1, Ansotegui IJ.

Abstract

PURPOSE OF REVIEW:

Component-resolved diagnosis (CRD) is an advanced tool capable of aiding the clinician in fine tuning the diagnosis of the causal allergens of a reaction with the added value of providing information of severity risk, potential cross-reactivity, and subsequently, guiding management measures. This review will focus on the advantages of CRD of anaphylaxis in clinical practice.

RECENT FINDINGS:

Research is continuously providing insight to which molecules are associated with genuine sensitization and/or potential severity risk for hymenoptera venom (Api m1, Ves v 1, Ves v 5, and Pol d 5), food allergy (seed storage proteins and nonspecific lipid transfer proteins), cofactor-enhanced food allergy (ω-5-gliadine, nonspecific lipid transfer proteins), red meat delayed anaphylaxis (α-gal), latex allergy (Hev b 1, Hev b 3, Hev b 5, and Hev b 6), and Anisakis allergy (Ani s 1, Ani s 4, Ani s 7, and Ani s 13); other molecules are primary associated with nonclinically relevant sensitizations, cross-reactivity, or mild reactions (carbohydrate determinants and profilins). New molecules, some minor allergens, are being identified as new potential biomarkers of severity.

SUMMARY:

The usefulness of CRD in anaphylaxis is self-evident, since it improves the recognition of sensitization profiles associated with specific clinical outcomes and provides information to guide further management.

PMID: 26945180 DOI: 10.1097/ACI.0000000000000261

SUMMARY:

Molecular allergy diagnosis is a novel tool just finding its place in the diagnostic work-up of allergic patients. It offers unique information when investigating the causes of anaphylaxis, and whenever possible, it should be considered as very useful in assessing the cause of reactions and guiding risk management in the future.

Curr Opin Allergy Clin Immunol. 2016 Oct;16(5):441-50. doi: 10.1097/ACI.0000000000000305.
Epidemiology of severe anaphylaxis: can we use population-based data to understand anaphylaxis?
Turner PJ, Campbell DE.

Abstract

PURPOSE OF REVIEW:

The observed increase in incidence of allergic disease in many regions over the past 3 decades has intensified interest in understanding the epidemiology of severe allergic reactions. We discuss the issues in collecting and interpreting these data and highlight current deficiencies in the current methods of data gathering.

RECENT FINDINGS:

Anaphylaxis, as measured by hospital admission rates, is not uncommon and has increased in the United Kingdom, the United States, Canada, and Australia over the last 10-20 years. All large datasets are hampered by a large proportion of uncoded, 'unspecified' causes of anaphylaxis. Fatal anaphylaxis remains a rare event, but appears to be increasing for medication in Australia, Canada, and the United States. The rate of fatal food anaphylaxis is stable in the United Kingdom and the United States, but has increased in Australia. The age distribution for fatal food anaphylaxis is different to other causes, with data suggesting an age-related predisposition to fatal outcomes in teenagers and adults to the fourth decade of life.

SUMMARY:

The increasing rates of food and medication allergy (the latter exacerbated by an ageing population) has significant implications for future fatality trends. An improved ability to accurately gather and analyse population-level anaphylaxis data in a harmonized fashion is required, so as to ultimately minimize risk and improve management.

PMID: 27490124
DOI: 10.1097/ACI.0000000000000305

SUMMARY:

A good review on the current epidemiology of anaphylaxis, highlighting the increased frequency of fatalities in teenagers and young adults.

J Allergy Clin Immunol Pract. 2016 Nov - Dec;4(6):1220-1226. doi: 10.1016/j.jaip.2016.06.003. Epub 2016 Jul 9.
Prospective Validation of the NIAID/FAAN Criteria for Emergency Department Diagnosis of Anaphylaxis.
Loprinzi Brauer CE, Motosue MS, Li JT, Hagan JB, Bellolio MF, Lee S, Campbell RL.

Abstract

BACKGROUND:

Anaphylaxis diagnostic criteria were proposed at the Second Symposium on the Definition and Management of Anaphylaxis. These criteria were 97% sensitive and 82% specific when retrospectively validated.

OBJECTIVE:

To prospectively evaluate the diagnostic accuracy of the National Institute of Allergy and Infectious Diseases/Food Allergy and Anaphylaxis Network (NIAID/FAAN) criteria for diagnosis of anaphylaxis in the emergency department (ED).

METHODS:

We conducted a prospective observational study of patients seen in our institution's ED from April 2010 to March 2013. Patients seeking care for an allergic reaction and possible anaphylaxis were enrolled. Patients and providers completed questionnaires regarding onset, trigger, and signs and symptoms. Records were reviewed independently and blindly by 2 board-certified allergist-immunologists, and their final diagnosis (anaphylaxis vs no anaphylaxis) was used as the reference standard. Two-by-two tables were built, and test characteristics were calculated.

RESULTS:

Among the 174 enrolled patients, 91 (52%) met the NIAID/FAAN criteria for anaphylaxis. The allergist-immunologists diagnosed 61 cases of anaphylaxis (35%), of which 58 (95%) also satisfied the NIAID/FAAN criteria. The interrater agreement between allergist-immunologists was substantial (κ = 0.7). Test characteristics (95% CIs) of the NIAID/FAAN criteria were as follows: sensitivity, 95.1% (85.4%-98.7%); specificity, 70.8% (61.4%-78.8%); positive predictive value, 63.7% (52.9%-73.4%); negative predictive value, 96.4% (89.1%-99.1%); positive likelihood ratio, 3.26; and negative likelihood ratio, 0.07.

CONCLUSION:

Prospectively, the NIAID/FAAN criteria continued to be highly sensitive (95%) but had lower specificity (71%) than on retrospective assessment. These criteria are likely to be useful for the diagnosis of anaphylaxis in the ED.

Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

KEYWORDS: Anaphylaxis; Diagnostic criteria; Test characteristics
PMID: 27406968
DOI: 10.1016/j.jaip.2016.06.003

SUMMARY:

The NIAID/FAAN diagnostic criteria for diagnosing anaphylaxis have been assumed by the major international and national guidelines. As in previous studies, this one validates their usefulness for diagnosing acute anaphylactic reactions and provides further evidence of their robustness.

J Allergy Clin Immunol. 2016 Dec;138(6):1652-1662.e7. doi: 10.1016/j.jaci.2016.03.053. Epub 2016 Jun 29.
Anti-hIgE gene therapy of peanut-induced anaphylaxis in a humanized murine model of peanut allergy.
Pagovich OE, Wang B, Chiuchiolo MJ, Kaminsky SM, Sondhi D, Jose CL, Price CC, Brooks SF, Mezey JG, Crystal RG.

Abstract

BACKGROUND:

Peanuts are the most common food to provoke fatal or near-fatal anaphylactic reactions. Treatment with an anti-hIgE mAb is efficacious but requires frequent parenteral administration.

OBJECTIVE:

Based on the knowledge that peanut allergy is mediated by peanut-specific IgE, we hypothesized that a single administration of an adeno-associated virus (AAV) gene transfer vector encoding for anti-hIgE would protect against repeated peanut exposure in the host with peanut allergy.

METHODS:

We developed a novel humanized murine model of peanut allergy that recapitulates the human anaphylactic response to peanuts in NOD-scid IL2Rgammanull mice transferred with blood mononuclear cells from donors with peanut allergy and then sensitized with peanut extract. As therapy, we constructed an adeno-associated rh.10 serotype vector coding for a full-length, high-affinity, anti-hIgE antibody derived from the Fab fragment of the anti-hIgE mAb omalizumab (AAVrh.10anti-hIgE). In the reconstituted mice peanut-specific IgE was induced by peanut sensitization and hypersensitivity, and reactions were provoked by feeding peanuts to mice with symptoms similar to those of human subjects with peanut allergy.

RESULTS:

A single administration of AAVrh.10anti-hIgE vector expressed persistent levels of anti-hIgE. The anti-hIgE vector, administered either before sensitization or after peanut sensitization and manifestation of the peanut-induced phenotype, blocked IgE-mediated alterations in peanut-induced histamine release, anaphylaxis scores, locomotor activity, and free IgE levels and protected animals from death caused by anaphylaxis.

CONCLUSION:

If this degree of persistent efficacy translates to human subjects, AAVrh.10anti-hIgE could be an effective 1-time preventative therapy for peanut allergy and possibly other severe, IgE-mediated allergies.

Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

KEYWORDS: IgE; Peanut allergy; food allergy; gene therapy; mouse model; omalizumab
PMID: 27372563
DOI: 10.1016/j.jaci.2016.03.053

SUMMARY:

This is a very interesting study on the potential effectiveness of gene transfer vector encoding for anti-hIgE to avoid anaphylactic reactions, demonstrated in this murine model of murine peanut allergy. It opens new potential therapeutic approaches in anaphylaxis despite its application in humans may still take some time.