Anaphylaxis: The Underrecognized Killer

EXECUTIVE SUMMARY

• The majority of anaphylaxis cases in infants and young children tend to be caused by food. In school-age children and adolescents, food is a common allergen, but more cases of reactions are from insect stings.
• Presenting symptoms can vary with age. Infants tend to present with hives and vomiting; school-age children with wheezing and stridor; and adolescents with “trouble swallowing,” “difficulty breathing,” and cardiovascular (CV) symptoms. In general, children more commonly present with skin and gastrointestinal symptoms.
• Biphasic reactions seem to be associated with a variety of triggers, but most often with a food allergen: food > medications > insect sting > other allergens or idiopathic causes.
• Most cases of fatal anaphylaxis are characterized by abrupt onset and progression of symptoms and by a short period of time (< 60 minutes) from exposure to the onset of symptoms. These reactions usually are uniphasic and present with fulminant symptoms that rapidly progress to respiratory arrest and/or shock with CV collapse.
• In a 2003 case series of fatalities in anaphylaxis, patients who died were placed in an upright position, leading to the “empty ventricle syndrome.” The recommendation is to lay the patient in Trendelenburg position or supine with legs passively raised.
• Epinephrine is the only medication shown to reduce mortality in anaphylaxis. It should be administered immediately once the diagnosis of an allergic reaction is made, and providers should not wait until there are overt signs of shock. It should be given intramuscularly in the anterolateral thigh in the vastus lateralis muscle and may be repeated every 5-10 minutes.
• While steroids are used in hopes that they will prevent biphasic or prolonged reactions, no randomized, controlled studies have confirmed or disproved their effectiveness in terms of decreased return visits or biphasic reactions.
• Most sources recommend an observation period of at least two hours after a dose of epinephrine, but preferably four to eight hours, particularly if there was moderate respiratory or CV compromise, severe asthma, or if the symptoms resolved promptly with medications. Longer observation periods have been advocated for anaphylaxis due to food because of their penchant to be severe and biphasic.

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This article will cover the presentation and emergency department (ED) management of allergic reactions in children, focusing on anaphylaxis. The current definition and recommended guidelines are reviewed.

— Ann M. Dietrich, MD, FAAP, FACEP, Editor

Cases

1. An 8-year-old boy presented to the ED after eating gluten-free chocolate cake. He threw up several times and complained of a sore throat, nausea, tongue swelling, and itching. En route, he developed facial swelling and urticaria.
2. A 5-year-old girl was brought to the ED from the radiology department. She was being sedated for a CT scan with IV contrast. She was induced with propofol without a problem. IV contrast had just been given when the girl developed hives and stridor. Her heart rate increased and her blood pressure dropped; she remained sleepy despite the propofol infusion being stopped.
3. A 3-year-old boy was brought in by ambulance after getting multiple yellow jacket stings. He has received epinephrine IM, diphenhydramine IV, methylprednisolone IV, and 20 mL/kg normal saline (NS) bolus intravenously with minimal improvement. On arrival, his heart rate was 63; respiratory rate, 40; blood pressure, 72/34; and O2 saturation, 94% on room air. He had facial and neck swelling, as well as urticaria on his chest and arms. He had stridor and decreased air entry on exam. He had good pulses but a capillary refill time of 4 seconds. He was sleepy but easily arousable.

Definition

An allergic reaction is a hypersensitivity reaction to an allergen and can range from mild and involving only one organ system to severe and life-threatening (i.e., anaphylaxis). Originally coined by Richet and Portier in 1902, anaphylaxis refers to a severe, life-threatening, systemic hypersensitivity reaction.^1,2 The definition of anaphylaxis has become increasingly more specific over the years. The most recent update (2006) from an expert panel on allergy and immunology at the National Institutes of Health defined anaphylaxis by specific involvement of multiple organ systems or by reduced blood pressure in the setting of exposure to a known antigen.^3-6 (See Table 1.) Anaphylaxis was divided into immunologic and non-immunologic reactions. Immunologic reactions were further classified as mediated by IgE-mast cell/basophil mediator release or by other immunologic mechanisms. Non-immunologic reactions, formerly called “anaphylactoid” reactions, were defined as reactions that clinically look like anaphylaxis, but are not IgE-mediated, resulting instead from direct mediator release from mast cells and/or basophils or by direct activation of the complement system. Obviously, these definitions cannot cover all possible anaphylactic presentations; by the same token, these symptoms can cover any number of diagnoses. In one study, when applied to reported cases of anaphylaxis, these definitions were found to have a low positive predictive value (69%) and a high negative predictive value (98%) compared to a diagnosis made by experienced allergists.⁷ Clinical acumen and provider judgment are essential to diagnosing anaphylaxis.

Epidemiology

Given the strict definition of anaphylaxis and the tendency of providers to underdiagnose it (either not recognizing it or coding it as something else), the cited prevalence and incidence of anaphylaxis are estimates at best.^2,5,8-9 The lifetime prevalence of anaphylaxis is estimated to be 0.05-2% for the general population.^{2,3,5-7,10-14} The annual incidence for all ages is estimated to be 49.8 per 100,000 person years.^10,15 More recently, there has been an increase in allergic disorders,^2,5,16-18 with rates of anaphylaxis more than doubled.¹⁹ Fortunately, less than one per million anaphylaxis cases worldwide are fatal.²⁰ In a recent study looking at fatal anaphylactic episodes in the United States from 2006 to 2009, the mortality rate was only 0.25-0.33%.²¹

Allergic reactions can occur at any age. In patients up to 15 years of age, anaphylaxis tends to be more common in males; however, it is more common in female patients older than 15 years of age.² The majority of anaphylaxis cases in infants and young children tend to be caused by food.²² In school-age children and adolescents, food is still a common allergen, but more cases of reactions are from insect stings. In adults, there are more reactions to medications/drugs. Many of these cases of allergic reaction and anaphylaxis present to the ED for care. In one review, the direct and indirect costs for allergies and associated anaphylaxis for food alone were estimated to be more than $500 million.²³

Pathophysiology

The prototypical anaphylactic reaction is IgE-mediated. As stated above, the older term “anaphylactoid” referred to non-IgE-dependent or non-immunologic events.^1,15 Classically, on exposure to an allergen, B cells begin to produce IgE, which diffuses through the body, occupying IgE receptors on mast cells and basophils. When allergens are encountered, they interact with the receptor-bound IgE and initiate an intracellular signaling cascade, causing these cells to release preformed mediators, enzymes, and cytokines.^1,24 In non-IgE-mediated reactions, immune complexes form between allergens and immunoglobulins, activating various immune cells and the complement cascade (e.g., drug reactions) or there is direct degranulation of mast cells/basophils (e.g., red man syndrome with vancomycin, urticaria with intravenous [IV] opiate infusion, or radiocontrast media reactions).^1,5 The end result of all of these reactions is the release of inflammatory mediators that create the clinical picture of allergic reactions and anaphylaxis.

A number of chemical mediators are released from mast cells and basophils.^{1,15,16,26,27} (See Figure 1.) Histamine probably is the most well-known mediator, causing flushing, hypotension, and headache via H1 and H2 receptors, and pruritus, rhinorrhea, bronchospasm, and tachycardia via H1 receptors. The severity and persistence of a reaction correlates with the amount of histamine released.

Although histamine can cause all of the symptoms in anaphylaxis, given the wide variety of presentations and courses, other mediators also may be important.²⁹ Tryptase activates the complement and coagulation pathways, as well as the kallikrein-kinin contact system, causing hypotension, angioedema, and both clot formation and lysis, resulting in disseminated intravascular coagulation in severe anaphylaxis. Usually, the severity of a reaction correlates with tryptase levels, except in cases of food allergy in which they can be low or normal.⁴ When histamine binds to H1 receptors, nitric oxide (NO) synthase is activated and converts L-arginine to NO via cyclic guanosine monophosphate.^2,28 NO has been implicated in hypotension via smooth muscle relaxation and in increased vascular permeability.

Other postulated mediators include platelet activating factor (PAF), arachidonic acid metabolites, carboxypeptidase A, and proteoglycans. PAF seems to correlate directly with the severity of allergic reactions to a better extent than histamine or tryptase.^4,26,30 Conversely, some mediators, such as chymase and sphingosine-1-phosphate, have anti-inflammatory and modulatory/counter-regulatory effects.

History

The key to diagnosing an allergic reaction is the recognition of a pattern of symptoms that appears after allergen exposure.⁶ As much detail about the reaction and antecedent events should be obtained, specifically the allergen (covering all exposures in the past 24 hours), the symptoms, any history of prior reactions, and the presence of any risk factors. See Table 2 for an example of key information in an allergic reaction to food.^4,24,31-33

In several studies that looked at the epidemiology of anaphylaxis, food allergies — usually to milk, eggs, peanuts, and tree nuts — predominated in infant and preschool-age children. In school-age children, allergies to insect stings begin to appear. In adolescents, this trend continues, and there are more reports of medication allergies, typically antibiotics and analgesics.^17,34 Outside of the hospital, anaphylaxis usually is food-mediated, most notably due to peanuts. In the hospital, latex and medications typically are the culprits.³⁵ Interestingly, in many studies, children who presented with anaphylaxis had a known allergy to the causative agent.^36,37 (See Table 3.)

Symptoms usually start minutes to hours (average 10 to 13 minutes) after an exposure. The rapidity of onset and severity of symptoms can vary, depending on the sensitivity to the allergen, route of exposure, quantity, and rate of administration, as well as a variety of risk factors.¹⁵ Such risk factors include:^2,5,6,31,38

• age (e.g., adolescents with their risk-taking behaviors);
• history of prior serious allergic reactions;
• intercurrent illnesses or activities (i.e., environmental activities);
• comorbidities (e.g., asthma, eczema, cardiovascular [CV] disease, mastocytosis, or neuropsychiatric or behavioral/developmental disorders);
• concurrent ingestion of other substances (e.g., ethanol, nonsteroidal anti-inflammatory drugs, β-blockers, monoamine oxidase [MAO] inhibitors, angiotensin-converting enzyme [ACE] inhibitors);
• other factors (e.g., exercise, menses, stress, occupational hazards).

Each of these risk factors affects how one responds both physiologically and behaviorally, and how one responds to treatments. The risk factors that have been associated with fatal anaphylactic episodes in multiple studies were exposure to nuts (peanuts or tree nuts), adolescent age, concomitant asthma (especially if poorly controlled), and a delay in epinephrine administration.^36,39 Unfortunately, the symptoms of an allergic reaction can vary between people and between episodes within one person; the severity of previous allergic reactions does not predict the severity of future reactions.^15,32,40

Of note, certain factors inadvertently can make a given anaphylactic episode worse.³¹ People experiencing an allergic reaction often isolate themselves while trying to treat their reaction; however, this keeps others from realizing that something is wrong and from helping. When bystanders do help, they sometimes prop up the victim in an effort to keep him/her awake and breathing. However, an upright posture actually may make things worse, as blood flows back to the heart and, subsequently, cardiac output can drop. The last factor that can worsen an episode illustrates how anaphylaxis can be difficult to diagnose. In exercise-induced anaphylaxis, the experienced symptoms can be attributed to the exercise itself, causing people to try and “power through” them, or, if they do realize that they are in trouble, try to run for help. In either case, they exert themselves even more, exacerbating their symptoms.

Signs and Symptoms on Physical Exam

Allergic reactions and anaphylaxis can present with a variety of symptoms, potentially causing problems with any organ system. The following discussion of symptoms is arranged by the ABCs: airway, breathing, circulation, disability (neurological), exposure (skin), and the remainder of the systems.

The airway of a patient suffering from an allergic reaction should be evaluated for its patency first. Inflammatory mediators can cause angioedema in oropharyngeal and/or laryngeal tissues, resulting in upper airway obstruction (stridor and hoarseness).^1,29 Other upper airway symptoms include sneezing, rhinorrhea, sore throat, tongue itching or swelling, and a sensation that the throat is closing or tightening.

The same angioedema in the lower airway can cause lower airway obstruction, resulting in cough, wheezing, mucus plugging, pulmonary edema, pulmonary hyperinflation, and dyspnea. The patient may develop respiratory distress, tachypnea, hypoxia, and ultimately, if untreated, asphyxia.^1,29,41

The CV symptoms are myriad. Although there have been reports of myocardial ischemia, conduction defects, dysrhythmias, and depressed cardiac function even after the other signs of anaphylaxis have resolved, the most notable and problematic circulatory symptom is shock.^1,27,29 Anaphylactic shock traditionally is classified as distributive shock, but it also has features of hypovolemic, cardiogenic, and obstructive shock.^{1,7,27,29,41,42} It is mainly distributive because of increased vascular permeability and capillary leak into the soft tissues. The volume shift can be significant, up to 35% within minutes. This, coupled with vasodilation, leads to a relative hypovolemia. The same inflammatory mediators that cause vasodilation also can depress myocardial function (cardiogenic shock). These ultimately lead to pulmonary vasospasm, a decreased left ventricular preload, and decreased cardiac output (obstructive shock). It is theorized that all of these effects on the CV system come together to cause an “empty ventricle syndrome” when a patient in anaphylaxis is placed in an upright position.⁴³ Specifically, peripheral vasodilation causes blood return to the inferior vena cava to decrease, resulting in a drop in preload, an unfilled left ventricle, a fall in cardiac output, loss of coronary artery perfusion, and ultimately myocardial infarction (MI) or pulseless electrical activity and death.

The response to this shock state usually is tachycardia. However, bradycardia also is possible later in the disease process. As venous return drops, a tension-sensitive receptor in the inferoposterior portion of the left ventricle is activated, which stimulates the vagus nerve, resulting in bradycardia; this is known as the Bezold-Jarisch reflex.^1,2,4,27,44 About 4% of cases, particularly insect stings, present with bradycardia.¹⁶ In one review of insect sting anaphylaxis, bradycardia was noted to precede hypotension. These cases responded well to IV epinephrine and IV fluids for the most part.⁴⁵

With these symptoms in mind, it is not surprising that some cases of anaphylaxis present as dizziness or syncope/collapse.^2,7,40 Other neurologic symptoms include headache, anxiety or sensation of impending doom, and agitation or confusion.⁵ However, if the symptoms are mild or there is little in the way of other symptoms, patients most likely will be awake and alert with a normal neurologic exam.

Perhaps the most common finding in anaphylaxis and allergic reactions is cutaneous, specifically urticaria in which lesions vary in size and are transient but recurring. In some cases, there may be only erythroderma rather than the classic urticaria. These patients often will appear flushed but will have paradoxically cool extremities. Another commonly affected system, the gastrointestinal (GI) system, may be affected and the patient may develop symptoms such as nausea, vomiting, and abdominal cramping.^7,40

Presenting symptoms can vary with age. Infants tend to present with hives and vomiting; school-age children with wheezing and stridor; and adolescents with “trouble swallowing,” “difficulty breathing,” and CV symptoms.⁴⁶ In general, children more commonly present with skin and GI symptoms while adults tend to present with CV symptoms.^24,47 One study looked at how often patients with anaphylaxis presented with various symptoms and found that 80-90% presented with skin and mucosa involvement, 70% with respiratory symptoms, 45% with GI symptoms, 15% with CV symptoms, and 15% with neurologic symptoms.^5,10,16,40 Many studies since have reported a similar distribution of complaints by system. This means that 10-20% of patients present without any skin findings.^6,16,29,48 It is important to remember that patients do not need to have cutaneous symptoms or shock to be diagnosed with anaphylaxis.⁴⁹ Indeed, part of the difficulty in managing allergic reactions and anaphylaxis is that both parents and providers have a hard time recognizing anaphylaxis. In one study, only 48% of parents could identify more than one symptom of an allergy and could manage the reaction. In another study, only 56% of physicians could appropriately diagnose and treat anaphylaxis.⁴⁷

Not all symptoms will present at the same time during an allergic reaction or anaphylaxis. There are three described phases of allergic inflammation: early, late, and chronic.¹⁸ The early phase occurs almost immediately after exposure (usually within 10 minutes) with the release of preformed mediators. This phase is characterized by increased blood flow, tissue swelling, itching, sneezing, wheezing, and abdominal cramps. It usually resolves within one to three hours. The route of allergen entry into the body affects time to development of symptoms, e.g. IV/intramuscular (IM) exposure causes symptoms in seconds to minutes while oral (PO) exposure causes symptoms in minutes to hours.¹ The late phase occurs within hours of the exposure (6-12 hours) and resolves by 24 hours. Typically, it is characterized by edema, erythema and induration of the skin, nasal congestion, and wheezing. The chronic phase, if it occurs, has persistent symptoms for days to years.

Clinically, allergic reactions also can be classified as uniphasic, biphasic, protracted, or delayed, depending on how long a patient has symptoms and whether the symptoms recur.^{1,3,6,7,25,24,50} Uniphasic reactions are the most common type of reactions. In these cases, the symptoms usually peak within 30 to 60 minutes and then resolve with or without intervention within another 30 to 60 minutes.⁵¹ There is some thought that when fluids begin to shift during a reaction, there is a compensatory release of counter-regulatory mediators that result in the resolution of the symptoms.¹ Biphasic reactions cause symptoms to develop acutely, just as in uniphasic reactions; however, after an apparent resolution of symptoms, they recur without re-exposure to the allergen. This happens in an estimated 23% of adult cases and 11% of pediatric cases. Typically, the symptoms recur within 12 hours, but sometimes can take up to 78 hours.^4,6,51,52 Protracted reactions involve symptoms that persist for hours, days, or even weeks. In delayed reactions, the symptoms start hours after the exposure, rather than within minutes. It is difficult to predict the rate of progression of symptoms or the ultimate severity. The initial severity of a reaction is not predictive of whether an episode will be uniphasic, biphasic, or protracted.⁵³ However, the more rapidly anaphylaxis develops, the more likely the episode will be severe and life-threatening.^4,6,7 It seems that, at least in terms of food anaphylaxis, if the symptoms do not develop immediately, then the reaction most likely will not be severe.⁵⁴

Two types of reactions have shaped much of what is done to manage cases of anaphylaxis: biphasic reactions and fatal anaphylaxis.

Biphasic Reactions. There are multiple theories as to why biphasic reactions occur, such as a later infiltration of T cells, a second wave of mast cell degranulation, a release of PAF, an artificial resolution of symptoms due to medications, and uneven antigen absorption. No one theory accounts for all cases.^51,52,55 Biphasic reactions seem to be associated with a variety of triggers, but most often with a food allergen: food > medications > insect sting > other allergens or idiopathic causes.⁵⁷ Other risk factors that come up repeatedly in studies are older age, severe initial symptoms requiring multiple doses of epinephrine or IV fluids for hypotension, less aggressive or delayed treatment (e.g., epinephrine given > 90 minutes after the start of symptoms), laryngeal edema or hypotension in the initial phase, delayed resolution of the initial symptoms, whether the allergen was ingested, any prior biphasic reactions or medication-induced anaphylaxis, a history of asthma or CV disease, and use of β-blockers.^51-53,58,59

Depending on the particular study, the time to the second phase can be, on average, between four to 10 hours.^{35,52,53,56-58} Because of this, observation periods to ensure that an acute reaction is not just the initial phase of a biphasic reaction can range up to 24 hours; but most sources recommend between four and eight hours from the start of symptoms.^52,53 Unfortunately, there is no consensus. The second phase may not necessarily resemble the first: It may be the same, better, worse, or even fatal.⁶⁰ More recent studies have looked retrospectively at biphasic reactions, applying the most recent definition of anaphylaxis and looking at how often the second phase is clinically important.^61,62 The authors concluded that biphasic reactions with clinically important second phases that required further intervention or resulted in death were rare (0.18% in one, 2.3% in another), which raised the question of whether prolonged observation periods (more than four hours) truly are warranted. The use of antihistamines or steroids to control the symptoms beyond the initial acute phase has not been shown to make a difference in biphasic reactions.⁵⁸

Fatal Anaphylaxis. Most cases of fatal anaphylaxis are characterized by abrupt onset and progression of symptoms and by a short period of time (< 60 minutes) from exposure to the onset of symptoms.²⁹ These reactions usually are uniphasic and present with fulminant symptoms that rapidly progress to respiratory arrest and/or shock with CV collapse. In children, respiratory arrest tends to be the cause of death; in adults, shock and CV collapse are the cause of death.⁶³ In terms of allergens, anaphylaxis to food tends to cause respiratory arrest, while anaphylaxis to insect stings and iatrogenic causes (i.e., medications, radiocontrast media) tends to cause shock.^6,64 In one review of pediatric anaphylaxis, the median time to development of symptoms was 10 minutes.²² In another retrospective study, the median times to cardiopulmonary arrest were five minutes after a diagnostic or therapeutic intervention, 10 minutes after an insect sting, and 30 minutes after ingestion of food.^6,64 It is not possible to predict which reaction will be fatal. Recurrent episodes do not always get worse over time.⁶⁵

Some risk factors that can increase the chance of having a severe allergic reaction/anaphylaxis have been identified repeatedly in a variety of studies.^44,63,66 These risk factors affect either the exposure to an allergen, the reaction itself, or the ability to treat the reaction. Adolescents tend to take risks and often cannot recognize when they are having an allergic reaction nor do they carry their epinephrine auto-injectors (EAI) at all times. Concomitant medical problems either make the patient more prone to developing an allergic reaction or cause symptoms to be more severe. Various medications either can increase uptake of an allergen or cause typical anaphylaxis treatment to be less effective. Of course, the delay or lack of epinephrine administration allows the symptoms to progress.

Differential Diagnosis

Multiple diagnoses can present with symptoms similar to anaphylaxis, but they usually involve only one organ system. As always, a careful history and physical exam usually can differentiate between them. In some cases, however, further testing is needed. (See Table 4.) The following discussion is organized by common anaphylaxis symptoms.

Generalized urticaria and angioedema can be seen with infections (especially parasitic or viral illness) and both autoimmune and non-immunologic diseases.⁶⁷ It also can be associated with physical stimuli such as heat or cold. One other disease process that presents as angioedema is C1 inhibitor deficiency (bradykinin-mediated or acquired angioedema) in which the patient has recurrent episodes of swelling not associated with itching or erythema; C4 and C1 esterase inhibitor levels are low in this disease.

Multiple disorders and syndromes can lead to flushing and urticaria, either as part of the disease process or as a result of histamine release. Flushing can be caused by ethanol, menopause, certain medications, and certain tumors (e.g., carcinoid tumors, GI tumors, or thyroid medullary carcinoma). Some cause flushing and urticaria after eating: scombroid poisoning, anisakiasis, ingestion of a caustic substance or monosodium glutamate, food poisoning, and pollen food allergy syndrome. Other syndromes are the result of excessive histamine release: mastocytosis, basophilic or acute promyelocytic leukemia, and hydatid cyst rupture. With many of these, a detailed history is all that is needed. For excessive histamine syndromes, blood tests and possibly imaging typically are required.

Respiratory symptoms, such as wheezing, can be the result of a number of diseases, most commonly an asthma attack. The clues that the wheezing may be due to anaphylaxis rather than an asthma attack are the involvement of more than one organ system and a temporal link (if noted) to an exposure to a likely or known allergen. Respiratory distress can be seen with a choking episode or foreign body aspiration, pulmonary embolus, pneumothorax, epiglottitis, and vocal cord dysfunction, among other conditions. Imaging studies usually are required to confirm these suspected diagnoses. Vocal cord dysfunction can mimic anaphylaxis with complaints of throat tightness and stridor. However, on exam, these patients do not have any visible angioedema, nor do their symptoms respond to anaphylaxis treatment. This diagnosis is made via laryngoscopy.^44,68

Cardiovascular and neurologic symptoms can mimic anaphylaxis with such complaints as chest pain, syncope, and shock. Of course, other etiologies such as arrhythmias, MI, cardiac disease, hemorrhage, subarachnoid hemorrhage, aortic catastrophe, panic attacks, and all the etiologies of the different types of shock must be considered. After stabilization of the patient, lab tests, an electrocardiogram, and most likely imaging (depending on the diagnosis) will be needed.

Treatment

Although treatment for allergic reactions and anaphylaxis may seem straightforward, it is based on expert consensus rather than evidence from research or trials since there have been no randomized, controlled studies without methodological problems.^6,7 The goal of treatment is early recognition and the use of epinephrine to halt the progression of the reaction to life-threatening respiratory or CV compromise. Although this is a simple goal, the problem is that one cannot predict the ultimate severity of a reaction, how rapidly it will progress, or whether it will resolve promptly, if at all.^6,70

For mild cases with limited symptoms that do not resolve spontaneously, symptomatic treatment with administration of an antihistamine, such as diphenhydramine or hydroxyzine, after removal of the allergen, may be sufficient.¹⁵ If there is a systemic reaction, administration of epinephrine IM is recommended to prevent progression of symptoms. Some recommend giving epinephrine even for mild episodes with single system involvement since the ultimate severity of a reaction cannot be predicted.^44,48

First-Line Therapies for Anaphylaxis. For anaphylaxis, there is less debate between experts about treatment.^{4,6,7,10,15,38,44,67,70-72} The allergen should be removed, if possible, to limit exposure. The provider should call for help and then assess and stabilize the patient per Pediatric Advanced Life Support (PALS) protocols. The patient can be placed in a supine position with the lower extremities elevated, unless there is respiratory distress or vomiting. In this case, the patient can be placed in a semi-recumbent position. If the patient happens to be pregnant, be sure to turn her on her left side.⁷³ Epinephrine should be given intramuscularly. If available, two large-bore IVs should be placed, and isotonic IV fluids should be given. If outside the hospital setting, the patient should be transported to an ED.⁷⁰ (See Figure 2 and Table 5.)

Certain aspects of this management should be highlighted. As mentioned before, body positioning is important in anaphylaxis. Based on a 2003 case series looking at fatalities in anaphylaxis, patients who died were placed in an upright position, leading to the “empty ventricle syndrome.”⁴³ The recommendation is to lay the patient in Trendelenburg position or supine with the legs passively raised. One study comparing these two positions noted that both positions improved cardiac output for hypovolemia, but only the passive leg lift had a sustained effect after one minute.^44,74

For airway and breathing management, early intubation should be considered if there is any concern for airway edema. The provider can see what effect epinephrine IM will have, as well as whether an inhaled beta-agonist will be of any help. However, the provider always must be prepared to intubate the patient or, in a worst-case scenario, perform an emergency cricothyroidotomy. As these are potentially very difficult airways, the most experienced person should intubate with backup by anesthesia or surgical services.⁴⁴

The goal of circulatory management is to optimize intravascular volume and vascular tone. Although epinephrine IM is the mainstay of treatment, IV fluids often are needed. If the patient is hypotensive, give rapid IV boluses of isotonic fluids, repeating as needed until the patient improves. Children may require upward of 30 mL/kg in the first few hours. Large volumes of NS can lead to a hyperchloremic metabolic acidosis, while Ringer’s lactate solution can cause a metabolic alkalosis. Some sources recommend switching fluids to avoid these complications if large volumes of fluids are used.^7,70 Other fluids (e.g., dextrose) and colloid expanders have not been shown to confer any advantage over isotonic fluids.

Epinephrine is the only medication that has been shown to reduce mortality in anaphylaxis.^3,75 Epinephrine should be administered immediately once the diagnosis of an allergic reaction is made, and providers should not wait until there are overt signs of shock.¹⁹ There have been no randomized trials looking at epinephrine as a treatment for anaphylaxis. Recommended doses have been based on tradition and expert consensus. Epinephrine works by decreasing mediator release from mast cells, preventing or reversing upper and lower airway obstruction, and preventing CV collapse by increasing preload and cardiac output via its α1, β1, and β2 agonist effects.^{5-7,16,49,70,76} It can cause anxiety, restlessness, headache, dizziness, palpitations, pallor, and tremor. Rarely does it cause ventricular arrhythmias, angina, MI, pulmonary edema, sudden increases in blood pressure, or intracranial hemorrhages.⁶ Patient factors that can affect the response to epinephrine include a history of CV disease (e.g., coronary artery disease, MI, arrhythmias), recent intracranial surgery, aortic aneurysm, uncontrolled hyperthyroidism or hypertension, or use of drugs such as MAO inhibitors, tricyclic antidepressants, or stimulants. That being said, there are no absolute contraindications to using epinephrine in anaphylaxis.⁷

The dose of epinephrine is 0.01 mg/kg/dose of the 1:1000 dilution (1 mg/mL), with a maximum dose of 0.5 mg in adults and 0.3 mg in children. It should be given intramuscularly in the anterolateral thigh in the vastus lateralis muscle and may be repeated every 5-10 minutes.^4,5,10,69,70 If possible, an exact dose of epinephrine should be given. The next section will discuss EAIs. Care must be taken to verify how much epinephrine is being given, particularly with the different doses and dilutions available. There have been many cases of iatrogenic morbidity due to mistakes in both dose and route.⁷⁷ Previously, epinephrine was given subcutaneously. However, a study compared concentrations of epinephrine in the plasma and tissues after a subcutaneous injection in the deltoid area vs. one intramuscularly in the vastus lateralis muscle, showing a more reliable and rapid rise in the serum levels when given intramuscularly in the vastus lateralis. There has not been a study comparing subcutaneous and IM injections in the vastus lateralis or IM injections in the deltoid muscle vs. the vastus lateralis muscle.^5,44,70

In severe anaphylaxis, when there may not be good perfusion of the muscles, IM doses of epinephrine may not be as effective.⁷⁰ In these cases, it may need to be given intravenously (see below). There is a higher incidence of hypertension and ventricular arrhythmias with IV epinephrine. Other routes of epinephrine administration have been tried, such as inhaled via metered dose inhaler and oral; however, they either have been too impractical or ineffective.^78-80

Multiple studies have reported that many cases of anaphylaxis have required more than one dose of epinephrine, typically noting rates from 5% up to 36%.^2,5,44,81-83 The reason for the additional doses is usually severe symptoms, persistent symptoms, or a biphasic reaction.^2,5,44,84 A more recent study specifically looked at risk factors for requiring multiple epinephrine doses and found that a history of anaphylaxis and the presence of diaphoresis or flushing and dyspnea were definite risk factors. A history of asthma and hypotension initially appeared to be risk factors, but they were not significant after multivariate analysis.⁸⁵

Epinephrine has been shown to decrease the risk of hospitalization; and delay in epinephrine administration is associated with an increase in the incidence of biphasic reactions or death.^{5,30,70,86,87} However, only 20-40% of cases get epinephrine.^36,49,88 In one study that looked at fatalities due to anaphylaxis, 62% had received epinephrine, but it was given prior to cardiopulmonary arrest in only 14% of these patients.⁶⁴ There are many barriers to epinephrine use that need to be addressed with patients and providers.

Epinephrine Auto-injectors. EAIs have made it possible to initiate life-saving treatment for anaphylaxis outside a medical facility. Several brands are available, with the two main types being syringe-based (e.g., Anapen) and cartridge-based (e.g., EpiPen). The steps to use either are similar. However, with syringe-based EAIs, there is an extra step of pressing a button to deploy the needle and give the dose; some of the dose may be deposited along the route of the needle. In cartridge-based EAIs, epinephrine is not released until the needle is in the tissue; also, the applied pressure needed to release the dose decreases the thickness of the soft tissue.⁸⁹

EAIs come in fixed doses: 0.15 mg, 0.3 mg, and 0.5 mg (in Europe and Australia). For patients weighing 15 kg to 25 kg, the 0.15 mg dose is recommended, although some experts advise this dose from 7.5 kg to 25 kg. For patients weighing > 25 kg, the 0.3 mg dose is recommended; for patients weighing > 50 kg, the 0.5 mg dose is recommended, if available.^{4,5,38,70,76,78,90} The dose can be repeated in five to 15 minutes. Since many cases need a second dose, some of these EAIs come in twin packs. Of note, the EAIs also have fixed needle lengths, which may cause issues in children at either end of the weight spectrum. In small children, the dose may be delivered into bone, rather than muscle, because these children do not have enough soft tissue.⁶⁶ Obese children may have too much soft tissue, so the needle may not be long enough to reach the muscle; this effect may be minimized by the force applied during the use of the EAI, which compresses the soft tissue.^4,5,23,71,76

Researchers have studied a couple of options — having the parents draw up the dose themselves or dispensing prefilled syringes — to address these issues. Simons et al looked at whether parents could draw up a correct dose in a calm setting, given an ampule and equipment, compared to healthcare providers. They found that parents took longer, drew up varying doses (a 40-fold range), had problems removing air from the syringe, and, in one case, crushed the ampule. In the same study, physicians drew up doses with an eight-fold variation, general ward nurses with three-fold variation, and ED nurses with two-fold variation. Because of this, the Canadian Society for Allergy and Clinical Immunology recommends giving 0.15 mg EAI for children < 10 kg since there currently are no other options and since the benefits outweigh the risks in anaphylaxis.^91,92 As for prefilled syringes, Rawas-Qalaji et al studied how long a dose could be kept in differing environmental conditions. They found that in a hot climate with low humidity, about 60% of the dose was present in three months. In a hot climate with high humidity, about 83% of the dose remained at four months. There was no difference whether the dose was kept in light vs. dark conditions.⁹³ Thus, neither of these options is particularly viable.

Other limitations of the EAI include expiration dates (12-24 months depending on the brand), need for training, availability, and high cost.^94,95 As in most situations that require patient education, it can be difficult to ensure that the patient and the caregivers understand and retain the important points. For EAI use, they need to know:⁷⁶

• where and how to give it, emphasizing that it can be given through clothes, taking care to avoid seams and items in pockets, and that they should avoid injecting their own finger;
• how to store it;
• to check to make sure the liquid is not discolored;
• to check the expiration date, refilling it promptly when expired.

It is better to give an expired EAI (as long as the liquid is not cloudy or discolored) than not to give epinephrine at all.^2,89

Beyond these limitations, various studies have found a variety of barriers. (See Table 6.) In one survey, despite patient education, only 30-44% of patients used an EAI correctly. Perhaps more alarming is that only 21% of providers were able to use an EAI correctly.⁹⁶ One study found that more anaphylaxis victims did not use their EAI than did. The ones who did use their EAI tended to have asthma, had respiratory or shock symptoms, or had a reaction to peanuts, fish, or an insect sting.Many took an H1 blocker or used their β-agonist inhaler before using the EAI. They reported that they did not know how to administer it, were worried about a needle stick or the medical waste (after its use), or did not have a prescription for an EAI (about 28%).⁹⁷ Although needlestick injuries do occur, they have not been seen to cause as many problems as initially feared. These present with local symptoms such as pallor and pain; there have been few, if any, reports of tissue necrosis or gangrene.^47,98-100

Second-Line Therapies for Anaphylaxis. Second-line therapies for anaphylaxis include antihistamines (H1 and H2 blockers), inhaled β2 agonists, and steroids. Although these often are given to treat allergic reactions, including anaphylaxis, their use is based on their utility in treatment of other allergic diagnoses, since their efficacy has not been tested in randomized, controlled trials.^6,101,102 They should never be given in lieu of epinephrine.^5,6,69 In one study looking at food-induced anaphylaxis, children who received epinephrine IM were less likely to need adjunct medications.⁸⁶

Antihistamines help with pruritus and urticaria by blocking the effects of histamine but do not reverse them or abort the anaphylaxis reaction.^4,5,7,18 Although they may help with any symptoms caused by histamine that has already been released, any improvement seen when they are used alone may be due to a release of compensatory mediators. This makes sense, since it would be impossible for antihistamines alone to block the effects of all of the inflammatory cascades activated in a reaction.¹⁰¹

H1 blockers have an onset of action of 30 to 40 minutes. The prototypical H1 blocker is diphenhydramine, dosed at 1 mg/kg/dose (max 50 mg/dose) and repeated up to 5 mg/kg/day. If given orally, the liquid formulation allows for faster action.¹⁰³ If given intravenously, note that rapid IV administration can cause hypotension. Other first-generation H1 blockers are chlorpheniramine, hydroxyzine, and promethazine. Second-generation H1 blockers also can be used: cetirizine, loratadine, and fexofenadine. These newer antihistamines cause less sedation and less cognitive/psychomotor impairment. They also have an onset of action of 30 to 40 minutes, but last for 24 hours. In studies comparing them, their effectiveness was as follows: fexofenadine > cetirizine > loratadine.¹⁰⁴ H2 blockers have been found to be helpful only with urticaria (e.g., ranitidine 1 mg/kg/dose IV [max 50 mg/dose]). The combination of H1 and H2 blockers has been found to be superior to the use of H1 blockers alone in controlling urticaria and, to a lesser extent, angioedema at two hours after their administration.^{2,4,48,63,105}

Inhaled β2 agonists (e.g., albuterol) are useful for bronchospasm that has not responded to epinephrine IM.⁴ They can help with bronchospasms via airway smooth muscle relaxation, but do not provide definitive treatment in anaphylaxis since they do not relieve mucosal edema.^5,48

Although steroids are used in hopes that they will prevent biphasic or prolonged reactions, no randomized, controlled studies have confirmed or disproved their effectiveness in terms of decreased return visits or biphasic reactions.^{4,5,7,4,48,106-108} The onset of action for steroids is several hours. Three commonly used steroids are methylprednisolone, prednisone, and prednisolone. Typically, they are continued for one to two days and then stopped without a taper. If there is a history of steroid use within the past several months, some consideration should be given to administration of stress-dose hydrocortisone during an anaphylactic episode. Other second-line agents can be used to help in specific cases. Hydroxyzine can be helpful in cases of cholinergic urticaria.¹⁵ Cyproheptadine is more useful in cases of cold urticaria.⁶⁷

Observation Period. The observation period after treatment must be individualized, taking into account the severity and duration of the event, the response to treatment, the pattern of any previous anaphylactic events, any medical comorbidities, patient reliability, and access to care should symptoms recur.⁴⁴ Most sources recommend an observation period of at least two hours after a dose of epinephrine, but preferably four to eight hours, particularly if there was moderate respiratory or CV compromise, severe asthma, or if the symptoms resolved promptly with medications.^6,7,38,48-50 Longer observation periods have been advocated for anaphylaxis due to food because of their tendancy to be severe and biphasic.⁴ Admission for observation for eight to 24 hours should be considered if any of the following is present:^{2,6,7,38,48,49}

• more severe symptoms;
• no prompt response to the epinephrine IM;
• airway obstruction (upper or lower) or hypoxia;
• need for multiple rounds of epinephrine;
• possibility of continued absorption or antigen (with ingestion);
• history of biphasic reaction;
• history of a mast cell disorder (e.g., mastocytosis).

Multiple studies have reported poor comprehension and compliance with these treatment recommendations. In a recent European study, 30% of anaphylactic cases in children initially were cared for outside a hospital by lay persons, not with epinephrine, but with antihistamines, inhaled β-agonists, and steroids. Epinephrine was given only in a fraction of cases, and 1.3% of the cases were life-threatening/fatal.³⁴ In a Canadian study, more than 25% of pediatric anaphylaxis cases presenting to a pediatric ED did not receive epinephrine prior to arrival. Those who did receive epinephrine ultimately needed less epinephrine in the ED.¹² In a review of food allergic reactions presenting to the ED, only 16% received epinephrine; 72%, antihistamines; 48%, steroids; and 33%, albuterol. Fifty-five percent of these reactions were classified as severe, but only 24% of these severe reactions received epinephrine.¹⁰⁹ A similar study by the same author looking at allergic reactions due to insect stings yielded similar results.¹¹⁰ These studies highlight the need for better education of patients, caregivers, and healthcare providers.

Refractory Anaphylaxis. Fortunately, death from anaphylaxis is relatively rare. The most common causes of fatality in one case series was airway obstruction and CV collapse. However, upright posture during treatment may have played a part, as discussed above. Of note, there was a failure to use epinephrine in many of the deaths.² In some cases, however, despite repeated doses of epinephrine IM and large-volume fluid boluses, symptoms of anaphylactic shock persist. In these cases, given the shock state, muscle perfusion most likely is not good; thus, the IM route for epinephrine would not work as well.^2,4,6,70 In these cases, an epinephrine drip can be used to treat shock. The typical pediatric dose is 0.1 mcg/kg/minute, titrating to effect in 0.05 mcg/kg/minute increments every three to five minutes, with a maximum dose of 1 mcg/kg/minute. Sometimes, an even lower dose (< 0.05 mcg/kg/minute) may be sufficient.¹¹¹

Although an IV bolus dose of epinephrine is not recommended unless the patient is in cardiopulmonary arrest, it can be given if an epinephrine drip is not available. Careful attention must be paid with bolus doses, as there is a higher risk of adverse CV events (e.g., arrhythmia, hypertension) and iatrogenic complications due to errors in dose calculations. In adolescents or adults, the dose for a bolus of epinephrine IV is 0.05 to 0.1 mg over at least three minutes. This is 1/10 or less than the arrest dose of epinephrine. The dose for children is not well-established.^5,7,48,70 If the patient is in cardiopulmonary arrest, advanced cardiovascular life support and PALS algorithms must be followed.^41,44,49,112 Prolonged resuscitation is encouraged in the setting of anaphylaxis, as there is a higher likelihood of good outcomes.^4,6 Should all interventions fail, extracorporeal membrane oxygenation can be used, especially since anaphylaxis is reversible.⁴⁹ At any point, should the patient’s airway need to be secured, keep in mind that the airway may be edematous and distorted and prepare accordingly.⁶

Should epinephrine not be sufficient, other vasopressors can be used: norepinephrine, dopamine, dobutamine, phenylephrine, and vasopressin.¹¹³ Studies have not shown any superiority of one vasopressor over another in this setting.^6,44 Other drugs can be of use in some cases, including tranexamic acid and methylene blue. Tranexamic acid can be helpful if there is intravascular coagulation caused by the various cascades activated by the inflammatory mediators.⁴ Methylene blue inhibits NO synthase and thus NO-induced vasodilation, increasing systemic vascular resistance.^4,7,114,115 It can be useful in anaphylactic shock with or without hypotension. A typical dose is a low dose (1.5 to 2 mg/kg), and improvement usually is seen in < 20 minutes. It should not be used in patients with pulmonary hypertension, acute lung injury, or G6PD deficiency; caution should be used if the patient is taking serotonergic agents. Of note, methylene blue will cause a false drop in oxygen saturation as a result of interference with the probe and can cause anaphylaxis itself.¹¹⁴

Other drugs can pose problems with anaphylaxis, either increasing the chance of a reaction or causing a problem with treatment. ACE inhibitors block compensatory responses to hypotension and decrease the ability to degrade bradykinin. MAO inhibitors, tricyclic antidepressants, and α-agonists augment the CV effects of epinephrine and interfere with its degradation. β-blockers can increase mediator release and impede some effects of epinephrine, as well as augment other effects such as α-agonist effects and reflexive vagotonic effects, leading to hypertension and cerebral hemorrhage.⁴⁴ The more problematic effects of β-blockers are persistent bradycardia and the blockade of the β-receptors that epinephrine uses to mediate its inotropic and chronotropic effects.^{5-7,16,44,48,116} Glucagon can be added if a patient taking a β-blocker is in anaphylactic shock and is not responding to epinephrine. The typical pediatric dose is 20 to 30 mcg/kg (max 1 mg/dose) given as a slow IV bolus over five minutes since rapid infusion can cause emesis; a drip then can be started at 5 mcg/minute, titrating to effect, up to 15 mcg/minute. If bradycardia is present and not responsive to epinephrine, atropine also can be used.⁶

Post-ED Care

Therapy with antihistamines and steroids is recommended to continue for a minimum of 48 hours, despite there having been no studies to see if patients actually need either medication after discharge once the symptoms resolve in the ED.^15,44,49,113 Beyond this, care after discharge should include avoidance of the allergen, treatment of chronic medical problems that might contribute to the allergic reaction, a prescription for an EAI, an Allergy Action Plan, a referral to an allergist, and a recommendation for a medical ID bracelet.^7,16 Thirty percent of children with allergic reactions will have another episode within seven years. There is a higher risk of another episode if there is a history of eczema, food allergies, or angioedema/urticaria.¹⁵

Education is key to the care of patients who have had an allergic reaction or anaphylaxis. It is a good idea to review what happened and stress that, untreated, an allergic reaction can be fatal. In particular, it should be stressed that symptoms may recur within 72 hours and that, if they do, an EAI should be given and the patient should return to the ED.⁶ It is important to discuss how to avoid an allergen, including the concepts of cross-reactivity and cross-contamination, and how chronic medical problems, such as asthma and eczema, can affect future allergic reactions.⁶ The other key items in the patient’s education involve the EAI and an Allergy Action Plan.

All sources state that, ideally, patients with allergies or who have suffered an anaphylactic reaction should receive a prescription (if not dispensed) for two EAIs, since up to 36% of cases need more than one dose of epinephrine IM.¹¹⁷ However, given the cost and availability of EAIs, various sources have tried to outline which patients absolutely should receive an EAI. One source recommends considering the risk of anaphylaxis, recurrence rate, and future severity of a reaction when writing a prescription for an EAI.¹¹⁸ The European Academy of Allergy and Clinical Immunology has stratified patients into those who have an absolute indication for an EAI and those who have a relative indication.^38,119 Those who have an absolute indication are those with a prior reaction to an unavoidable trigger, exercise-induced anaphylaxis, idiopathic anaphylaxis, a previous systemic reaction to an insect sting, a mast cell disorder, and persistent asthma with food allergies. Those who have a moderate indication are those with a peanut or tree nut allergy, a reaction to a small quantity of food, teenagers with food allergies, and those who live far from a medical facility.

Sadly, few patients receive a prescription for an EAI.³⁶ In a recent Canadian study, 60% of patients who had an anaphylactic episode did not have an EAI.¹² Even if an EAI is given, only a fraction actually use it. Depending on the study, the percentage of patients with anaphylaxis who receive epinephrine can range from < 20% to 39.3%.^36,40,49 One survey of U.S. adults who reported having an episode of anaphylaxis reported that only 11% had given themselves epinephrine. Most of these had more than two episodes of anaphylaxis. Of the participants, 52% never received a prescription for an EAI, and, at the time of the study, 60% did not currently have an EAI.¹²⁰ Reasons for not giving epinephrine in anaphylactic episodes included failure to recognize anaphylaxis, assumption that an episode would be mild, history of spontaneous recovery in a previous episode, reliance on oral H1 blockers or asthma rescue inhalers, needle phobia, lack of an EAI, and concerns about side effects of epinephrine.¹²¹ If possible, these points should be addressed prior to discharge from the ED to remove as many obstacles to EAI use as possible.

An anaphylaxis emergency action plan lists common symptoms and signs of anaphylaxis, how to recognize anaphylaxis promptly, and how to self-inject epinephrine. An example of an action plan can be found at http://www.foodallergy.org/file/emergency-care-plan.pdf.⁴⁸ The action plan should be taught to the child, as well as all of the child’s caregivers.

The last piece in care of these patients is referral to an allergist. This is important not only to confirm the diagnosis of anaphylaxis, but also to identify the allergen and provide counseling on how best to avoid future reactions.³¹ In one study, 35% of patients who were diagnosed with anaphylaxis had their diagnosis changed after evaluation by an allergist.⁴⁸ In another study looking at people who followed up with an allergist after treatment for anaphylaxis in the ED, 7% had anaphylaxis ruled out, 32% with an unknown trigger had a trigger identified, 6% with a suspected trigger had a trigger in a different category identified, and 2% were diagnosed with a mast cell disorder.¹²² Optimal time to testing is three to four weeks after an episode. Typically, either skin tests or serum IgE levels are evaluated. These tests only reveal sensitization to an allergen, not whether a specific trigger will cause anaphylaxis.^5,69 If these tests are negative and there is a high suspicion for an allergy, a provocation test can be conducted. However, if there is a convincing history of anaphylaxis, provocation tests are contraindicated.^5,31 If an allergen is identified and avoidance of the trigger is not feasible, immunomodulation is available for certain allergens, such as venom immunotherapy for insect stings.^5,16

Current Research

Current research in anaphylaxis and allergic reactions has been focused on improving primary prevention via immunotherapy, such as sublingual or oral food immunotherapies. There has been some promise in these trials, but it is unclear whether these therapies are inducing true tolerance or just temporary desensitization.¹²³ There also are promising results in lab studies with a Chinese herbal therapy called Food Allergy Herbal Formula 2 for food allergies.³³ Beyond these interventions, researchers are looking for new lab tests that would screen for anaphylaxis, not just sensitization to allergens, and are working on new EAIs, trying to address the various barriers to their use. For example, one of the latest EAIs has voice prompts to guide the patient through administration of the epinephrine dose, much like an automated electronic defibrillator. In the meantime, studies have shown time and again that healthcare providers still need to improve recognition, treatment, and patient education for allergies and anaphylaxis.

Conclusion

Allergic reactions are reactions to an allergen that are mediated by inflammatory mediators such as histamine and tryptase. Anaphylaxis is a severe, potentially fatal, allergic reaction. Specific criteria for anaphylaxis have been delineated by national and international expert consensus. Mild, single-system symptoms, such as hives, may be treated with antihistamines alone. Treatment for severe or multisystem symptoms, such as anaphylaxis, includes removal of the allergen, keeping the patient in a recumbent position with slight elevation of the legs, stabilization of the ABCs, and administration of epinephrine IM as quickly as possible. Oxygen and rapid IV boluses of isotonic fluids also may be indicated. There have been no randomized, controlled studies to prove or disprove the efficacy of antihistamines, steroids, or even epinephrine. The recommendations for treatment are based on expert opinion and utility in other allergic diseases. A good number of reactions are biphasic; thus, it is recommended to observe anaphylaxis patients for four to eight hours at a minimum and to consider admission for 24 hours for more severe reactions requiring multiple or repeated interventions.

Every patient with an allergic reaction should be discharged from the ED with an allergy action plan, an EAI, and a referral to an allergist. Education on the appropriate use of an EAI and avoidance of the suspected allergen should be completed prior to discharge from the ED. Treatment plans and prognosis differ depending on the allergen and any medical history the patient may have. Education and follow-up with an allergist are critical to the long-term management of these patients.

Case Conclusions

1. The 8-year-old boy who ate the gluten-free cake was suffering from anaphylaxis. It turned out that he had a tree nut allergy, and the gluten-free cake had ground cashews in it. He received a dose of epinephrine IM, an albuterol nebulizer treatment, diphenhydramine IV, methylprednisolone IV, and an NS bolus and experienced improvement of almost all of his symptoms. However, his symptoms kept recurring 30-60 minutes after treatment. He received two more doses of epinephrine IM and NS boluses before he was admitted to the ICU on an epinephrine drip. He was discharged later the next day after being off of the epinephrine drip for several hours. He was sent home with an EAI and a two-day course for prednisolone, diphenhydramine, and ranitidine, as well as a recommendation to follow up with his allergist.
2. The 5-year-old girl who was undergoing a CT with IV contrast was suffering from a contrast reaction. She had an upper airway obstruction and was in hypotensive shock. She was given epinephrine IM, diphenhydramine IV, methylprednisolone IV, and a rapid NS bolus. Although her CV symptoms stabilized, her respiratory symptoms persisted despite a second dose of epinephrine IM. She was intubated and admitted to the ICU on an epinephrine drip. After several hours, she was able to be extubated.
3. The 3-year-old boy who was stung by yellow jackets was in anaphylactic shock. His exam was notable for hypotension and bradycardia, which can be seen in anaphylaxis caused by insect stings, as well as for upper air obstruction and hypoxia. Despite another dose of epinephrine IM, IV fluids, and ranitidine in the ED, his symptoms persisted. He was intubated and placed on epinephrine drip with gradual improvement over the next 24 hours. He was discharged home the next day on a steroid taper, diphenhydramine, ranitidine, and an epinephrine auto-injector. The allergist who evaluated him in the hospital had an appointment with him several weeks later to talk about venom immunotherapy.

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