Anaphylaxis is a serious, life-threatening allergic reaction that can occur suddenly without warning. In children and adolescents, the leading cause of anaphylaxis is exposure to food allergens. Recently, the American Academy of Pediatrics (AAP) published 2 clinical reports that discuss guidance on appropriate epinephrine use for anaphylaxis and developing an emergency action plan for patients at risk.
Anaphylaxis is a serious, life-threatening allergic reaction that can occur suddenly without warning. In children and adolescents, the leading cause of anaphylaxis is exposure to food allergens. Maintenance of pediatric healthcare provider knowledge in food allergy and anaphylaxis is critical to prevent fatalities from serious allergic emergencies. Recently, the American Academy of Pediatrics (AAP) published 2 clinical reports that discuss guidance on appropriate epinephrine use for anaphylaxis and developing an emergency action plan for patients at risk. Pediatric healthcare providers also need to recognize unmet medical needs and barriers to successful anaphylaxis management in their patients. This article reviews current issues in real-world practice and new guidance from the AAP on epinephrine use and a written emergency action plan for pediatric patients with anaphylaxis.
Anaphylaxis is a serious systemic reaction that is unpredictable in nature and that can occur suddenly after contact with any number of substances that elicit allergic (immunoglobulin E [IgE]-mediated) or nonallergic (non–IgE-mediated) reactions.1 It is defined by a wide range of clinical symptoms, some of which may be very severe and, in some cases, potentially fatal.2
Anaphylaxis is a growing problem with the largest incidence in children and adolescents. The leading cause of anaphylaxis in the young is food allergy. An estimated 5.9 million children in the United States have food allergy.3 Moreover, 38% of those children have a history of severe reactions. As the prevalence of food allergy and anaphylaxis increases in children, the administration of epinephrine at home, schools, day camps, restaurants, and when traveling will become increasingly necessary.
There is a significant and constant need to prepare pediatric healthcare providers and their patients/caregivers to manage anaphylactic episodes. The AAP has recently released 2 clinical reports, one on the use of epinephrine for an allergic emergency,4 and the other on emergency action planning.5 The criteria for a diagnosis of anaphylaxis, the need for auto-injectable epinephrine, the role of an emergency action plan, and barriers to successful management are reviewed.
Anaphylaxis should be highly suspected in any individual presenting with both cutaneous and respiratory symptoms.2 A reaction is defined by the acute onset of generalized urticaria, itching or flushing, swollen lips-tongue-uvula, and at least 1 of the following: a) dyspnea, wheeze-bronchospasm, stridor, reduced lung function, hypoxemia; or b) reduced blood pressure or collapse, syncope, incontinence.
Anaphylaxis is also highly probable if more than 2 of the following occur rapidly after exposure to a likely allergen: a) generalized urticaria, itch-flush, swollen lips-tongue-uvula; b) dyspnea, wheeze-bronchospasm, stridor, reduced lung function, hypoxemia; c) reduced blood pressure or collapse, syncope, incontinence; or d) persistent nausea, crampy abdominal pain, and vomiting. Importantly, hypotension alone (following exposure to a known allergen) may be the manifestation of anaphylaxis and would be sufficient for diagnosis and treatment.
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Compared with adults, pediatric patients demonstrate differences in comorbid conditions, risk factors, and clinical manifestations. Although respiratory findings frequently have been observed in preschool-aged children, which are similar in adults, cardiovascular symptoms rarely have been reported in this age group (although this is possibly attributed to inadequate blood pressure monitoring).6 In infants, hives and vomiting are the more common symptoms. Careful monitoring for changes in pallor and subtle behaviors such as scratching and drooling, which can reveal the presence of itching and difficulty swallowing, respectively, can signify important allergic symptoms. Children may also verbalize that they “do not feel right” or have “a burning tongue,” which may suggest an allergic reaction but is sometimes ignored.
Certain factors increase the risk for anaphylaxis, particularly in children and adolescents. For example, asthma is likely the most significant risk factor for death from food-related anaphylaxis.7 Teenagers are also at higher risk for fatal reactions because of a tendency to deny their condition, not recognize serious symptoms, take risks while eating, and forget to carry their epinephrine auto-injector (EA). Furthermore, 22% of anaphylaxis cases involving high school students were associated with an unknown trigger, compared with 14% in grade school students and 15% in middle school students.8 Compounding factors should be considered when assessing risk and establishing management strategies.7
Ensuring that children and adolescents follow up with a specialist is significant as well, because confirming the diagnosis and positively identifying the triggering allergen is important. In a review of patients admitted to a large pediatric tertiary care center for food-induced anaphylaxis, the majority of patients admitted for food-induced anaphylaxis received auto-injector training and a prescription at discharge, but 31% had no plan for allergy specialty follow-up.9 To illustrate the importance of this point, one study determined that undergoing a follow-up allergy evaluation revealed an inaccurate diagnosis or misidentified trigger in nearly 35% of patients with suspected anaphylaxis.10
Available guidelines strongly recommend epinephrine as first-line treatment for patients with anaphylaxis.2 Appropriate management requires prompt administration of intramuscular epinephrine. There is neither contraindication to nor substitute for epinephrine as first-aid treatment for an anaphylactic episode. During an anaphylactic reaction, epinephrine should be administered intramuscularly into the anterolateral thigh, followed by placement of the patient in a recumbent position, and provision of supplemental oxygen and/or the administration of intravenous (IV) fluid, if needed, based on severity of symptoms.2 Patients also should be observed closely after calling for emergency medical services (EMS).
In addition to intramuscular epinephrine, in some cases, patients may need supportive therapies including alpha-adrenergic agonists, IV fluid resuscitation, H1 and H2 antihistamines, corticosteroids, and potentially vasopressors or glucagon.2
NEXT: Attributes of current EAs
A second injection of epinephrine also may be necessary to resolve anaphylaxis. For very severe reactions, 2 or more doses may be required. However, when response to the initial dose of epinephrine is suboptimal, a second injection of epinephrine is preferred over adjunctive treatments. If necessary, the epinephrine dose may be repeated every 5 to 15 minutes.
Discrepancies in real-world practice related to the treatment of anaphylaxis need to be addressed. Availability of epinephrine to patients with anaphylaxis is alarmingly low (52% never receiving a prescription for EAs despite previous episodes),11 as is the administration of epinephrine by EMS providers for patients with anaphylaxis symptoms (36% to 54%).12,13 This suggests that there is a significant need for more education on anaphylaxis and when to use epinephrine, even among first responders.
In a review of pediatric emergency department (ED) records for anaphylactic reactions over a 5-year period at a large academic hospital, collective data indicated that a greater percentage of patients were treated with antihistamines and steroids than were treated with epinephrine.14 Also, H1 receptor antagonists and steroids were administered in 92% and 89% of cases, respectively. The potential administration of these adjunctive agents as first-line therapies is concerning given that they are characterized by a therapeutic onset longer than the time to respiratory and/or cardiovascular arrest during anaphylaxis.
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Reports by Greenberger15 and Pumphrey16 have demonstrated that death from anaphylaxis can occur quickly. Greenberger noted that approximately 50% of deaths occurred within the first 60 minutes of allergen exposure, while Pumphrey noted that the median time to respiratory or cardiac arrest was 5 minutes for iatrogenic reactions to medications (eg, IV antibiotics/nonsteroidal anti-inflammatory drugs [NSAIDS]), 15 minutes for venom, and 30 minutes for foods. Reported onset of action for antihistamines, and thereby their use, is incompatible with the reported times to cardiac arrest from anaphylaxis. Progression of anaphylactic reactions is unpredictable, even for the most experienced clinician, so caution is warranted if adjunctive agents are used as first-aid treatment; eg, life-threatening respiratory symptoms can occur after skin symptoms have waned.
Appropriate route of delivery of epinephrine is also an important consideration in practice. A survey of pediatric emergency medicine physicians identified through the American Board of Pediatrics and American Board of Medical Specialties membership databases revealed that although 93.5% correctly identified epinephrine as the treatment of choice for anaphylaxis, only 66.9% reported using the recommended intramuscular route.17 Prompt and appropriate delivery of epinephrine cannot be overemphasized.
Different EA design is a major determinant of successful administration during a reaction. Table 1 shows select attributes of available EAs. Although there are no prospective comparative data with different EAs during actual anaphylactic reactions, there have been studies done to test the “usability” of several EAs.
NEXT: Barriers of successful treatment of anaphylaxis
One study conducted with 3 different EAs evaluated the ability of mothers of children aged 0 to 18 years, diagnosed with food allergy, to properly use their EA.18 In this study, users of pen-style EAs experienced errors including failing to remove all safety caps or using the wrong end of the device, which caused accidental digital injections. Importantly, changes to the prescribing information for pen-style EAs were made in 2015 per the US Food and Drug Administration (FDA) because of reported lacerations and embedded needles in children’s legs with the use of EpiPen devices.19 In the same study above, Auvi-Q users had the highest success rate during simulated allergic emergencies (26/28, 93% Auvi-Q vs 39/80, 49% pen-style devices; P<0.001).18
Healthcare provider education
Across the continuum of healthcare providers, there will be more who never treated a patient with anaphylaxis than those who have. Improving knowledge about anaphylaxis and its treatment is an important, ongoing goal. In one study, 56% of US-based pediatricians (random national sample; n=1130) had knowledge deficits that may affect their ability to accurately diagnose anaphylaxis correctly and treat it with epinephrine.20
To improve healthcare provider knowledge, a wallet card from the American Academy of Allergy, Asthma, and Immunology (AAAAI) with critical information about anaphylaxis and its treatment was prospectively designed and tested as a tool for education on anaphylaxis with a group of pediatric resident physicians.21 The study demonstrated that pediatric resident physicians in the group receiving education about the wallet card were more likely than the control group to recognize anaphylaxis symptoms, name asthma as the most common comorbid disease in children with fatal or near-fatal anaphylaxis, and recall the names of available EAs and their fixed premeasured dosages of epinephrine. The wallet card can be downloaded from the AAAAI in English and Spanish: bit.ly/AAAAI-anaphylaxis-card.
Patient education and EA training
Not understanding when to use an EA is one of the most common barriers experienced during real-world reactions. Guidance on when to inject for children or adolescents experiencing an allergic reaction is shown in Table 2.
Education on allergen avoidance can help patients prevent most inadvertent exposures to known allergic triggers. Although not always possible, improved food labeling has enabled a greater likelihood of avoiding food triggers. Indeed, nearly half of inadvertent food-induced anaphylaxis cases can be linked to prepackaged labeled products.22 Likewise, prevention of cross-contamination of food should be highlighted as this is another frequent cause of accidental exposure.
Epinephrine auto-injector training can prepare patients to self-manage anaphylactic episodes. In general, patients and family members should be trained or refreshed on their EA’s instructions with each refill. However, despite a relatively straightforward process, errors are common in administration for a variety of reasons. To successfully address this issue, it is recommended that individuals practice the injection technique using “trainers” and review the manufacturer’s educational materials. Patients/families can also watch videos or review pictures of the instructions for their EA. Importantly, once patients are prescribed an EA and trained on their device, substitutions should be discouraged. Consistent use of the same device will help patients and their caregivers administer epinephrine as swiftly and safely as possible in case of an emergency.
Recent trends suggest that food allergy and anaphylaxis continue to grow in children, which necessitates reinforcement of best practices in pediatric anaphylaxis care. Maintaining an acceptable level of knowledge on anaphylaxis recognition and treatment, so that everyone involved in the care of children and adolescents with anaphylaxis can act when necessary, is critical to preventing fatalities.
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Furthermore, EAs should be with the patient at all times, whether they are self-carried or carried by parents or caregivers. Review your school’s policies stating whether a child is allowed to carry his/her own EA and at what age. It is also important that caregivers (eg, grandparents, babysitters, camp staff, parents of friends) are knowledgeable on the use of the patient’s specific EA.
The AAP has provided guidance for pediatric healthcare providers on the appropriate use of epinephrine and the importance of developing a written emergency action plan for patients with anaphylaxis. This is the first time the AAP has published and made available an allergy and anaphylaxis emergency plan. The authors recommend that these guidances be adopted into current practice. Lastly, recognizing and addressing unmet medical needs and barriers to successful treatment of anaphylaxis in pediatric patients is necessary to improve patient outcomes.
Medical writing and editorial assistance was provided by Sean M. Gregory, PHD, Hybrid Healthcare Communications LLC, and funded by kaléo, which had no role in the development, review, or final approval of the manuscript.
1. Sampson HA, Muñoz-Furlong A, Campbell RL, et al. Second symposium on the definition and management of anaphylaxis: summary report-second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium. Ann Emerg Med. 2006;47(4):373-380.
2. Lieberman P, Nicklas RA, Randolph C, et al. Anaphylaxis-a practice parameter update 2015. Ann Allergy Asthma Immunol. 2015;115(5):341-384.
3. Gupta RS, Springston EE, Warrier MR, et al. The prevalence, severity, and distribution of childhood food allergy in the United States. Pediatrics. 2011;12891:e9-e17.
4. Sicherer SH, Simons FER; Section on Allergy and Immunology. Epinephrine for first-aid management of anaphylaxis. Pediatrics. 2017;139(3):e20164006.
5. Wang J, Sicherer SH; Section on Allergy and Immunology. Guidance on completing a written allergy and anaphylaxis emergency plan. Pediatrics. 2017;139(3):e20164005.
6. Rudders SA, Banerji A, Clark S, Camargo CA Jr. Age-related differences in the clinical presentation of food-induced anaphylaxis. J Pediatr. 2011;158(2):326-328.
7. Smith PK, Hourihane JO, Lieberman P. Risk multipliers for severe food anaphylaxis. World Allergy Organ J. 2015;8(1):30.
8. White MV, Hogue SL, Bennett ME, et al. EpiPen4Schools pilot survey: occurrence of anaphylaxis, triggers, and epinephrine administration in a US school setting. Allergy Asthma Proc. 2015;36(4):306-312.
9. Strothman K, Scherzer D, Mustillo P, et al. Inpatient management and discharge planning for children admitted for food-induced anaphylaxis. J Allergy Clin Immunol. 2015;135:AB204.
10. Campbell RL, Park MA, Kueber MA Jr, Lee S, Hagan JB. Outcomes of allergy/immunology follow-up after an emergency department evaluation for anaphylaxis. J Allergy Clin Immunol Pract. 2015;3(1):88-93.
11. Wood RA, Camargo CA Jr, Lieberman P, et al. Anaphylaxis in America: the prevalence and characteristics of anaphylaxis in the United States. J Allergy Clin Immunol. 2014;133(2):461-467.
12. Tiyyagura GK, Arnold L, Cone DC, Langhan M. Pediatric anaphylaxis management in the prehospital setting. Prehosp Emerg Care. 2014;18(1):46-51.
13. Carrillo E, Hern HG, Barger J. Prehospital administration of epinephrine in pediatric Anaphylaxis. Prehosp Emerg Care. 2016;20(2):239-244.
14. Huang F, Chawla K, Järvinen KM, Nowak-Wegrzum A. Anaphylaxis in a New York City pediatric emergency department: triggers, treatments, and outcomes. J Allergy Clin Immunol. 2012;129(1):162. e3-168.e3.
15. Greenberger PA, Rotskoff BD, Lifschultz B. Fatal anaphylaxis: postmortem findings and associated comorbid diseases. Ann Allergy Asthma Immunol. 2007;98(3):252-257.
16. Pumphrey RS. Lessons for management of anaphylaxis from a study of fatal reactions. Clin Exp Allergy. 2000;30(8):1144-1150.
17. Grossman SL, Baumann BM, Garcia Peña BM, et al. Anaphylaxis knowledge and practice preferences of pediatric emergency medicine physicians: a national survey. J Pediatr. 2013;163(3):841-846.
18. Umasunthar T, Procktor A, Hodes M, et al. Patients’ ability to treat anaphylaxis using adrenaline autoinjectors: a randomized controlled trial. Allergy. 2015;70(7):855-863.
19. Brown JC, Tuuri RE. Lacerations and embedded needles due to EpiPen use in children. J Allergy Clin Immunol Pract. 2016;4(3)549-551.
20. Krugman SD, Chiaramonte DR, Matsui EC. Diagnosis and management of food-induced anaphylaxis: a national survey of pediatricians. Pediatrics. 2006;118(3):e554-e560.
21. Hernandez-Trujillo V, Simons FE. Prospective evaluation of an anaphylaxis education mini-handout: the AAAAI Anaphylaxis Wallet Card. J Allergy Clin Immunol Pract. 2013;1(2):181-185.
22. De Schryver S, Clarke AE, La Vieille S, et al. C-Care: impact of labeling in food induced anaphylaxis in children treated at the Montreal Children’s Hospital. J Allergy Clin Immunol. 2015;135(2):AB201.
23. Sicherer SH, Mahr T; American Academy of Pediatrics Section on Allergy and Immunology. Management of food allergy in the school setting. Pediatrics. 2010;126(6):1232-1239.