Evaluation and Management of Anaphylaxis in the Emergency Department

By Kyley J. Wyss, MD, FACEP, and Derek M. Sorensen, MD, MHPE, FACEP

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Introduction

For emergency physicians, anaphylaxis can be a challenging diagnosis to make. International guidelines have been left intentionally vague because of the range of presentations that may occur with anaphylaxis. Unfortunately, the diverse manifestations of life-threatening anaphylaxis may lead to delays in life-saving treatment because there is not a specific set of criteria for diagnosis. The current knowledge gap is a major issue for patients, emergency providers, and the medical community.

Patients may present to the emergency department with a range of hypersensitivity reactions, including mild pruritis and urticaria to fulminant cardiorespiratory collapse. Anaphylaxis is the most deadly presentation among the spectrum of hypersensitivity reactions encountered in the emergency department. It is important that the emergency clinician remembers that patients with anaphylaxis may not present with a chief complaint of “allergic reaction.”

This article will present the most current information for diagnosing allergic reactions and anaphylaxis, and how to treat them properly. In addition, the article will discuss the often-uncertain treatment decisions that come with a presentation of isolated urticaria or angioedema.

The diagnostic criteria for anaphylaxis, let alone the best course of treatment, are highly debated topics that require further research.

Epidemiology

The worldwide incidence of anaphylaxis is increasing.¹ At least 1.6% of the population in North America will have an anaphylactic reaction in their lifetime, with a lifetime prevalence of 0.5% to 2.0% worldwide.^2,3 The reason for the increase is not known precisely, but food allergy prevalence in North America is increasing more rapidly than in European countries.¹ In the United States, the rate of visits to the emergency department for anaphylaxis increased by 101% between 2005 and 2014.⁴ This increase was most prominent in children ages 5-17 years.⁴ It should be noted that epidemiological studies are challenging because the diagnosis of anaphylaxis can be difficult and its incidence may be underrepresented.

Most cases of anaphylaxis are caused by exposure to an unknown trigger (57%). Identifying the trigger may take time and some detective work, especially regarding food allergies. The most commonly identified triggers are food (27%), medications (12%), and insect venom (4%).⁴ (See Table 1.) Adults tend to have a more severe presentation than children, with features including hypotension and respiratory distress.⁵ Adults also are hospitalized after an anaphylactic reaction more frequently than children.⁴ The concurrent use of alcohol or recreational drugs may make the diagnosis of anaphylaxis more difficult to identify and may lead to a deadly delay in the administration of epinephrine.⁶ Infants and toddlers who cannot verbalize their symptoms often are treated less aggressively than older children.⁷

Mortality from food-induced anaphylaxis is rare, with 31 fatalities reported to a comprehensive registry maintained by members of the American Academy of Allergy, Asthma & Immunology (AAAAI) and the Food Allergy and Anaphylaxis Network between 2001 and 2006.⁸ In this registry, deaths from a high suspicion of anaphylaxis from a food allergen were more prevalent in males (61%) and in adolescents/young adults.^8,9 Most patients had a known history of food allergies and asthma.^6,8 In a study of drug-induced anaphylaxis, older patients with more cardiovascular comorbidities had a higher rate of fatal anaphylaxis reactions.⁹ Most deaths were associated with prolonged time from the start of the reaction to epinephrine administration.⁸ While food-induced anaphylaxis is more common in general, drug-induced anaphylaxis seems to have the highest mortality rate.⁶

There appears to be a propensity for anaphylactic reactions in those with a medical history of asthma and eczema.¹⁰ Although the rate of fatal drug-induced anaphylaxis is on the rise, food- and venom-induced anaphylaxis rates are stable.⁹

Etiology

The most commonly identified triggers for anaphylaxis are foods, medications, insect stings, and allergen immunotherapy.¹¹ (See Table 1.) In both adults and children, food is the most common trigger for anaphylaxis.⁵ Overall, studied risk factors for anaphylaxis in general include exercise, alcohol use, nonsteroidal anti-inflammatory drug (NSAID) use, acute infections, stress, and perimenstrual status.⁹ These factors are associated with anaphylaxis at highly variable rates among different studies. Still, about 20% of cases of anaphylaxis are idiopathic.¹²

Foods are the most common triggers for anaphylaxis. The most common food triggers are peanuts, tree nuts, milk, and shrimp.⁸ Other common food allergens include soy, chickpeas, bananas, nectarines, wheat, eggs, and seeds.¹¹ (See Table 2.) However, any food, seasoning, or spice can trigger an anaphylactic reaction. In addition, patients can acquire a life-threatening allergy to red meat from the bite of the Lone Star tick (alpha-gal syndrome). As our diet consists increasingly of store-bought over home-prepared food, it is becoming increasingly common for individuals with known allergies to be exposed to their inciting allergens in their homes.

Any drug can lead to an allergic reaction. The most common drugs that cause allergic reactions are beta-lactam antibiotics, salicylates, sulfa drugs, vancomycin, and NSAIDs.¹¹ (See Table 3.) Deaths from drug allergies were most frequently associated with beta-lactam and cephalosporin antibiotics, general anesthetics (namely neuromuscular-blocking agents), and radiocontrast agents.⁹

The healthcare system predisposes patients to some other common allergens, such as latex, vaccines, radiographic contrast material, and blood products.¹¹ Other common allergens include hymenoptera stings (i.e., bee and wasp stings), insect parts (i.e., ingested bugs, tick heads), mosquito bites, and molds.

Anaphylaxis to venom has a propensity to occur in men, typically of white race.⁹ Most deaths associated with venom anaphylaxis have occurred after honeybee stings, but insect parts, such as ingested insects, tick heads left under the skin after improper removal, or mosquito bites, also can present a risk for allergic reaction or anaphylaxis.⁹

Exercise-induced anaphylaxis is a disorder in which individuals develop hypersensitivity with exercise.¹³ In 30% to 50% of cases, the reaction is food-dependent and occurs with a combination of certain foods and exercise.¹³ One theory is that exercise may increase absorption of certain food allergens through increased intestinal permeability.⁹ It also has been reported in combination with medications (namely NSAIDs), extreme temperatures, menstrual cycles, and environmental allergens.¹³ Anaphylaxis in the setting of exercise has been found to be as prevalent as milk allergy in some prospective studies.¹⁴

The COVID-19 messenger ribonucleic acid (mRNA) vaccine was released in the United States during the height of the COVID-19 pandemic in December 2020, and its use was widespread in an effort to curtail the pandemic. While there was a high number of initial reports that the vaccine carried an increased risk of anaphylaxis, recent data show that the rate of anaphylaxis to the COVID-19 mRNA vaccine and boosters actually is similar to that of any other common vaccine product.¹⁵ As with other vaccines, the current Centers for Disease Control and Prevention (CDC) guidelines at the time of this writing advise caution with administration to patients who have known allergies to ingredients of the vaccine or the vaccine itself.¹⁵

Pathophysiology

The body’s inappropriate response to a harmless antigen is referred to as hypersensitivity.¹¹ Any agent that can produce a sudden degranulation of mast cells or basophils can induce anaphylaxis.¹¹ The resulting symptoms are manifested in organ systems with high expressions of mast cells, namely the cutaneous, respiratory, cardiovascular, and gastrointestinal systems.¹²

In the gastrointestinal tract, mast cells coated with immunoglobulin E (IgE) are the chief mediators of food protein allergic reactions.¹¹ There are non-IgE-mediated inflammatory reactions mediated by allergen-specific lymphocytes, such as in allergic contact dermatitis, as well as immunoglobulin G (IgG) antibodies such as in serum sickness.¹⁶

Angioedema is the acute onset of asymmetrical, non-pitting swelling of the skin, mucous membranes, or both.¹⁷ It typically involves the upper airway and digestive tract but is not limited to these areas.¹⁷ Angioedema may be allergic in nature and would follow a similar pathological pathway as aforementioned.

However, angioedema also may occur secondary to complement or bradykinin pathways. This is seen in patients experiencing hereditary angioedema or angioedema related to angiotensin converting-enzyme (ACE) inhibitor medication use. The pathophysiology of angioedema mediated by bradykinin will not be discussed here. ACE inhibitor-related angioedema occurs in 0.1% to 0.7% of patients taking ACE inhibitors, with an increased incidence in African Americans.¹¹ Hereditary angioedema can present similarly, but the underlying cause is different. A large portion of cases of angioedema are associated with ACE inhibitor use, which may account for this reaction typically appearing in an older age group than anaphylaxis.¹⁷

Clinical Features

Patients presenting with an allergic reaction can range from those with no or mild symptoms to those who arrive in extremis. Although it is recognized that systemic hypersensitivity reactions occur with a spectrum of severity, there has not been a well-studied classification system developed for the emergency department provider to aid in decision making.¹⁸ This makes allergic reactions challenging to recognize, report, and study. Moreover, developing uniform treatment action plans for these rare events also is challenging.

Urticaria and diffuse erythema typically are recognized easily and may be early manifestations of an allergic reaction. However, 10% of patients will not develop any cutaneous signs, which may make the diagnosis of anaphylaxis more difficult. In one study, only about half of health professionals could correctly identify anaphylaxis.^19,20

The presenting symptoms of anaphylaxis are varied. The clinical criteria for anaphylaxis are as follows (see Table 4):

Urticaria, generalized itching or flushing, or edema of the lips, tongue, uvula, or skin developing over minutes to hours and associated with at least one of the following:

• respiratory distress or hypoxia;
• hypotension or cardiovascular collapse; or
• associated symptoms of organ dysfunction (i.e., hypotonia, syncope, incontinence).

Two or more signs or symptoms that occur minutes to hours after allergen exposure, including:

• skin or mucosal involvement;
• respiratory compromise;
• hypotension; or
• persistent gastrointestinal cramps or vomiting.

Consider anaphylaxis with known allergen exposure and developing hypotension.¹¹

A history may or may not be available. Ideally, a known exposure will have occurred to a known allergen at a known time. However, in most cases, a specific allergen is not found.⁴

Urticaria is a cutaneous hypersensitivity reaction to an allergen and may be found both as one of a constellation of symptoms in anaphylaxis or as a single symptom with its own diagnosis. Similarly, angioedema, while certainly concerning for its impact on the patient’s ability to breathe, is not in itself anaphylaxis, but rather a mucocutaneous hypersensitivity reaction (usually of the upper airway) and can be found as either a symptom of anaphylaxis or its own pathology.

Diagnostic Studies

No specific diagnostic studies are required to diagnose an allergic reaction, but physicians may order indicated studies if the diagnosis is unclear. Elevations in tryptase and histamine levels may be present in the blood, but clinical utility for these studies remains poor.²¹ Testing for antigen sensitivity should be performed in the outpatient setting by an allergist after the initial anaphylactic reaction.²²

Differential Diagnoses

Given the often vague presenting symptoms of allergic reactions and anaphylaxis, a broad differential is a good approach when considering the treatment and stabilization of the patient with suspected anaphylaxis. Vasovagal syncope is the most common presentation that can imitate the symptoms of anaphylaxis.²² Patients may present with symptoms similar to acute coronary syndrome, arrhythmia, airway obstruction or epiglottitis, seizures, and many other possibilities.¹¹ Because patients present with sudden shortness of breath, pulmonary embolism may be considered. Especially when there is no historical information or a history of an inciting event, it is important not to anchor on anaphylaxis while keeping in mind that early intervention is extremely important in its management.

Management

Stabilization of the patient in anaphylactic shock requires removal of the allergen and administration of epinephrine. This should be done in conjunction with the usual priorities: evaluating the airway and assessing breathing and circulation. Consider using the mnemonic “ABCDE” when assessing a patient with suspected anaphylaxis: airway, breathing, circulation, decontamination, and epinephrine. (See Table 5.)

The initial and most important treatment for recognized anaphylaxis with or without cardiovascular compromise or collapse is intramuscular (IM) epinephrine given in the lateral thigh.²³ Previously, epinephrine was given subcutaneously, but it is better absorbed after IM injection. This should be repeated every five to 10 minutes according to response, or if a relapse occurs.^11,24 A shorter interval is permissible if the clinician believes that another dosage is necessary.²⁵ The correct IM dosing is 0.01 mg/kg of 1:1,000 (1 mg/mL) solution, up to 0.3 mg in adults and 0.15 mg in children < 30 kg.¹¹ Epinephrine has been demonstrated to be underused for treatment of anaphylaxis in numerous studies, largely because of misdiagnosis and unfamiliarity with its use in this disease process.^7,26-28

The route of administration is imperative to effective management; when compared to IM, blood concentrations of subcutaneously administered epinephrine take longer to reach peak blood levels. When epinephrine is injected intramuscularly into the lateral thigh, peak plasma levels of epinephrine are reached faster than when injections are given either subcutaneously or intramuscularly in the deltoid.^25,29 If the patient arrives to the emergency department with an intravenous (IV) line in place or if staff members are quickly able to establish IV access, IM epinephrine up to three doses still is recommended because of the increased potential for side effects such as arrhythmia when epinephrine is given IV.³⁰

If the patient remains refractory to treatment with multiple doses of IM epinephrine (typically three, but there is not currently supported literature to recommend an exact number), or when the patient has signs of cardiovascular collapse, administer an IV bolus of epinephrine 5 mcg to 10 mcg (or 0.2 mcg/kg) for hypotension and 0.1 mg to 0.5 mg for cardiovascular collapse.²⁵ If the patient remains refractory, an infusion should be started at 1 mcg/min and titrated to effect. Additional vasopressors may be subsequently initiated if necessary, and Advanced Cardiac Life Support practices should be initiated in the event of cardiac arrest.

If angioedema appears to be causing any signs of respiratory distress (uvular edema, audible stridor, hypoxia, etc.), intubate the patient early.¹¹ Note that most patients with angioedema, especially those with mild symptoms, typically have self-limiting courses without airway compromise and most do not require intubation.³¹ Ventilator management in the anaphylactic patient should be patient-driven, keeping in mind that these patients may have significant bronchospasm and are at higher risk of barotrauma with large tidal volumes.

Another consideration in the intubated patient may be the use of propofol for sedation. Physicians may have heard that in patients with peanut allergies, the soya oil excipient of propofol can be cross-reactive. However, this oil is refined and is unlikely to contain enough soya protein to produce an allergic response. However, the product literature for propofol does list peanut allergy as a contraindication, so consideration for other sedating medications is strongly recommended.³²

Removal of the offending agent may require a full body examination (i.e., in the case of bee stings, the stinger must be removed). Gastric lavage for ingestions is not recommended currently for foodborne allergens.¹¹

Hypotension in anaphylaxis is related to distributive shock and should be treated with IV isotonic crystalloids in standard bolus dosing: 1 L/hour to 2 L/hour in adults (3 L to 5 L+ may be required) and 5 mL/kg to 10 mL/kg in the first five minutes, maximum 30 mL/kg in the first hour in children.^11,30 Adding an alternative vasopressor with the epinephrine infusion, such as norepinephrine or vasopressin, should be considered in epinephrine- and fluid-resistant hypotension, and should be titrated to response.^22,30 For continued refractory cases, consider using extracorporeal membrane oxygenation (ECMO) when it is available.³⁰

In addition, it also may be beneficial to keep the patient in a supine position, with legs in the air if possible, to improve venous return to the heart.¹² In fact, in some studies, upright positioning in anaphylactic shock has been found to be associated with increased mortality.²⁵ Refrain from having the patient lie flat if the patient is having shortness of breath or vomiting, but attempt to keep the legs elevated even if the patient cannot lie flat.²⁵

Epinephrine administration prior to arrival in the emergency department, either from a home autoinjector or administered by emergency medical services (EMS) personnel, is associated with a decreased need for epinephrine in the hospital.¹⁰ There is evidence that epinephrine administration does not significantly benefit hemodynamics once shock is fully developed in anaphylaxis.³³ This evidence suggests early epinephrine administration is crucial in the management of anaphylaxis. This demonstrates the importance of providing a patient presenting with anaphylaxis with an autoinjector or a prescription for an autoinjector at the time of their discharge.

Other pharmacological agents should be administered, most with more “theoretical benefit” than “studied benefit.” These are considered second-line treatments, since most have a lengthy onset of action.

Nebulizer treatment with albuterol is recommended in patients with signs of bronchospasm.³⁴ Consider the potential risk of exacerbating hypotension in patients in shock with further beta agonist-induced tachycardia. Supplemental oxygen should be administered in patients with respiratory symptoms or those requiring multiple doses of epinephrine.³⁵ Racemic epinephrine is not currently recommended and should not be used as a substitute for IM epinephrine because of the delay in reaching satisfactory blood levels. However, it may be beneficial in patients presenting with upper respiratory angioedema and stridor.³⁶

H1 antagonists such as diphenhydramine (Benadryl) may be administered orally (PO), IM, or IV.³⁴ The onset of action is one to three hours. This class of medications likely has little benefit in controlling all but the cutaneous symptoms of anaphylaxis (urticaria and angioedema).¹² It has little effect on blood pressure.²⁵ The recommended dosage of diphenhydramine is 25 mg to 50 mg (PO/IV/IM) in adults and 1 mg/kg, maximum 50 mg, in children.²⁵ In some studies, H2 antagonists, such as ranitidine or cimetidine, used in combination with H1 antagonists have been shown to treat cutaneous symptoms better.²⁵

Steroids may be given intravenously after the initial resuscitation.³⁴ Oral steroids prescribed after discharge also are reasonable and may be especially efficacious in patients with concomitant asthma.³⁴ However, there is little to no evidence of their efficacy in treating allergic reactions or preventing biphasic reactions.¹² Subsequently, there is high variability of their administration timing and dosing.³⁷ Dosing should be 1.0 mg/kg/dose to 2.0 mg/kg/dose equivalent of methylprednisolone every six hours IV.²⁵ Oral prednisone can be given in 1.0 mg/kg up to 50 mg for mild reactions.²⁵ The duration of outpatient therapy with oral steroids remains controversial.

Glucagon has a theoretical benefit in patients taking beta-blocker medications with refractory hypotension and bronchospasm not responsive to epinephrine.²⁵ The dosing for administration is 1.0 mg to 5.0 mg over five minutes, with an infusion of 5 mcg/min to 15 mcg/min titrated to response.²⁵ When using glucagon, it is important to consider airway protection and safety because administration of glucagon may induce vomiting.²⁵

In patients with a history of contrast or iodine allergy, pretreatment with IV crystalloid bolus and/or steroids (50 mg prednisone given 13 hours, 7 hours, and one hour prior to injection) and antihistamines (50 mg diphenhydramine and 300 mg ranitidine orally or IV one hour prior) has been shown to be beneficial in preventing allergic reaction.²² The clinician must weigh the risks and benefits of the historical reactions, the ability to give any of these medications prior to contrasted studies, and the need for these diagnostic studies to be conducted.²²

While the emergency physician will not find the test helpful, obtaining a tryptase level 30 minutes to two hours after the initial reaction and trending at 24 hours may assist in differentiating anaphylaxis as the cause of the patient’s presentation. Obtaining this laboratory value may be most appropriate in uncertain cases in which the patient is to be admitted to the hospital for trending.^38,39

Treatment: Urticaria

The management of an urticarial reaction involves the removal of the offending agent and symptomatic treatment.¹¹ Patients can be treated with H1 antihistamines as a first-line agent.¹¹ Again, the use of steroids is common but is without significant supporting data, as is the use of H2 antihistamines.¹¹ Epinephrine should be considered only in severe or refractory cases of urticaria.¹¹

Treatment: Angioedema

The treatment of angioedema is similar to that of an urticarial reaction unless a nonallergic form of angioedema triggered by ACE inhibitor use or hereditary angioedema is suspected.¹¹ Neither of these forms will respond to anaphylaxis treatment since their pathophysiology is bradykinin- or C1 esterase inhibitor-mediated, respectively.¹¹ Treatment of both non-allergenic forms is largely supportive and expectant.

ACE inhibitor-mediated angioedema symptoms may last hours to days, with little data to support the use of either C1 esterase inhibitor at 1,000 U IV or icatibant (a bradykinin-2 receptor antagonist) at 30 mg subcutaneous (SC). The symptoms of hereditary angioedema may be shortened with the use of C1 esterase inhibitor at 20 U/kg IV, icatibant at 30 mg SC, or ecallantide at 30 mg SC.¹¹ Fresh frozen plasma can be used in place of C1 esterase inhibitor when it is not available.¹¹

Complications

Death by anaphylaxis is rare and typically occurs secondary to circulatory collapse and/or respiratory arrest.³⁵ One study of fatal anaphylactic reactions found that only 14% of patients who died from anaphylaxis had received epinephrine prior to arrest, alluding to the importance of early administration of epinephrine.¹⁴

Biphasic reactions, or a return of allergic symptoms after complete resolution of anaphylaxis without repeated exposure to the antigen, are a feared complication of anaphylaxis, with incidences of 1% to 23% of cases of anaphylaxis reported.¹⁸ Risk factors for the biphasic reaction include severe initial reactions (especially the symptoms of laryngeal edema or hypotension), delayed administration of epinephrine, or a delayed response to antigen exposure.¹⁸ However, the treatment for a biphasic reaction should be the same as for the initial anaphylactic reaction. Consider a patient’s risk factors for biphasic reactions when determining disposition. Most studies report a mean time to onset of the secondary reaction of more than eight hours, with a maximum of 72 hours, after resolution of the initial reaction.⁴⁰

While epinephrine administration is the definitive treatment for anaphylaxis, it is not without complications. The safety profile of epinephrine use in anaphylaxis has been studied, with one paper showing an overall side effect rate of about 21.6%. In that study, the side effects primarily included mild and transient effects, such as tremors, palpitations, and anxiety. These effects are more frequent in the adult population.⁴¹ More severe adverse events due to epinephrine administration, such as chest discomfort, elevated blood pressure, or electrocardiogram (ECG) changes, were associated with IV administration rather than IM administration.⁴¹ Coronary artery vasospasm-inducing ST-segment elevations and troponin elevations after administration have been reported.⁴² One feared effect is epinephrine use in the setting of patients using nonselective beta-blocker medications, since this theoretically could cause coronary artery vasospasm.⁴³ However, this potential and infrequent complication should not delay epinephrine administration in patients experiencing anaphylaxis on beta-blocker medications.⁴³

The need for multiple doses of epinephrine in the emergency department has been found to have a higher association with a delay in the administration of epinephrine or administration in the emergency department rather than in the prehospital setting.⁴ In addition, the need for multiple doses was associated with anaphylaxis after triggers with strong evidence for more severe anaphylactic reactions, including peanuts, tree nuts, and milk.⁴⁴

Kounis syndrome occurs when anaphylaxis causes coronary artery spasm.⁴⁵ Patients often present with chest pain, but this may be ignored by the clinician at presentation of patients in extremis from anaphylaxis. Consider obtaining an ECG for patients with chest pain. Patients with prolonged chest pain or an abnormal ECG should be observed and have troponin measured.

Disposition

The post-anaphylactic patient with a quick response to epinephrine administration should be observed for four to six hours.¹⁸ The patient should be monitored for signs and symptoms of continued or biphasic allergic response and should be treated appropriately if these occur. The patient with a delayed onset of allergic symptoms after allergen exposure, a delayed administration of epinephrine, or a poor response to treatment should be observed longer or observed in an inpatient setting because of the increased risk of biphasic reaction.¹⁸ Other considerations for inpatient observation may include access to medical care, uncertainty of the risk of allergen re-exposure, or parental discomfort with discharge. If the patient is hospitalized, consider consulting an allergist early if this is the hospital’s practice.

If there are ongoing signs of anaphylaxis despite treatment, if an epinephrine drip has been started for the patient, or if the patient is ventilated, intensive care unit admission generally is appropriate.

After four to six hours of emergency department observation, patients who remain symptom-free can be discharged home with an epinephrine autoinjector and instructions for its use. Recent reports state that 60% of individuals who experienced anaphylaxis were not equipped with epinephrine at home.² Epinephrine autoinjectors are under-prescribed after discharge, with one paper finding that they were prescribed only 31.7% of the time after criteria for anaphylaxis on emergency department admission were met.⁴⁶ There is much to be said for educating all patients on the use of their autoinjectors prior to discharge, since one study found that only 30% to 40% of patients with autoinjectors were able to use them properly.³⁴ Also inform patients that autoinjectors typically expire after about one year, and their efficacy may be compromised after that date.

The cost for autoinjectors is high, and supplies can be low in some geographic areas. Generic autoinjectors are available, although they also have been in short supply. The autoinjector often comes in a two-pack, allowing the patient to give a second dose if symptoms worsen while they seek medical help. Patients should be encouraged to carry the injectors in a place that is always accessible, such as a purse, camera bag, etc. Autoinjectors are permitted in carry-on luggage on airplanes.

Prescribing epinephrine autoinjectors to patients with allergic reactions but without anaphylaxis, such as those who arrive at the emergency department with urticaria only, is not recommended currently.¹⁹ The dose of epinephrine contained in autoinjectors is not without risk or side effects. Providers in the emergency department tend to prescribe oral antihistamines every six hours for the first 24 hours in such circumstances; however, there are little to no data to support this practice. H1 antihistamines may be prescribed on an as-needed basis for ongoing cutaneous symptoms.

Most emergency medicine providers continue to prescribe scheduled steroids and antihistamines after resolution of anaphylaxis despite the lack of evidence that steroids affect urticaria or other allergic symptoms, including repeat anaphylaxis.⁴⁷ Steroids are theorized to decrease the risk of biphasic reactions, but studies have not shown actual benefit.¹⁸

Consultation with an allergist is strongly recommended, but referrals to allergists are made only about 45% of the time, and patients actually see an allergist much less often.^46,48 There are many benefits to the patient with a history of anaphylaxis in seeing an allergy specialist. Patients with anaphylaxis to bee stings can be successfully desensitized over several months. Those with food allergies and their families may benefit from dietetic consultation as well, which will assist in avoiding allergens in their diets.⁴⁹ For children, requesting that parents share this education with schools and daycare facilities will reduce the risk of anaphylactic reactions at these locations.^49,50 Those with drug-induced allergies should receive written documentation of the likely medication, if possible, to assist with communication between patients and their future providers.

There is inadequate evidence to suggest that taking antihistamines or H2 antagonists prior to exercise is protective for likely exercise-induced anaphylaxis.³² It has been estimated that about half of exercise-induced anaphylaxis is associated with ingesting certain foods. Delaying exercise for five hours after eating is recommended to prevent reactions.¹² Physicians in the emergency department should recommend avoiding exercise as one would with any other trigger, prescribe an autoinjector to be carried at all times and when exercise cannot be avoided, and refer to an allergist.

Summary and the Future of Anaphylaxis in the Emergency Department

Current proposals for diagnostic criteria have been found to have good sensitivity but poor specificity, and they lack prospective validation.⁵¹ There is no well-studied set of clinical criteria to delineate definitively between an acute allergic reaction and anaphylaxis. Therefore, emergency department physicians do not have standardized guidelines for management. In the future, a more defined set of criteria for anaphylaxis and allergic reactions will benefit patients and the physicians who treat them. This will allow for improved disease recognition and earlier treatment with epinephrine. In the meantime, have a high index of suspicion for anaphylaxis as an etiology of a patient’s presentation, know the signs and symptoms of anaphylaxis, and give epinephrine early after weighing the risks and benefits of administration.

Underreporting due to the knowledge gap and subsequent misdiagnosis of anaphylaxis will continue to make research of this disease complex.⁵² Interestingly, difficulty studying anaphylaxis is even hindered by discharge coding. One study found that half of their study population would have been missed for research if coded incorrectly.⁵³ Providers can assist in future research by specifying a known allergen in a patient’s chart. The fluid language used when describing an “allergic reaction” vs. “anaphylaxis” and “anaphylactic shock” can be confusing to patients, can lead to miscommunication between providers, and can make studying the disease process difficult due to inappropriately named diagnoses. The allergy community has called to revise the current nomenclature to enhance the descriptive vocabulary.⁵⁴

Further studies also are needed to help practitioners decide whether, when, and how much antihistamines and steroids to administer and prescribe. Allergic reactions often do not meet proposed criteria for anaphylaxis, and physicians are left with vague recommendations and data on treatment with antihistamines, steroids, or novel treatment modalities.

In general, the earlier epinephrine is administered, the better the outcome. Since first responders often are the first to see the patient during an allergic reaction, educating EMS personnel on recognizing anaphylaxis and implementing protocols for early epinephrine administration are vital to reducing overall morbidity, mortality, and length of hospital stays.

In a study on North American emergency department concordance with current guidelines in anaphylaxis, researchers found that epinephrine treatment occurred 49% of the time, epinephrine autoinjector prescriptions were given 57% of the time, referral to an allergist occurred 12% of the time, and instructions to avoid the offending allergen occurred 24% of the time.⁵⁵ A patient presenting with anaphylaxis received three of four of the guideline recommendations only 16% of the time.⁵⁵ A better understanding of the proper approach to recognizing anaphylaxis, treatment, and disposition is needed. While this article cannot clearly state a straightforward approach to diagnosing and treating the spectrum of allergic presentations, understanding that the disease itself is not straightforward and still shrouded in mystery is imperative to the emergency practitioner. It is an important differential to consider in several possible presentations, and one of the most common life-threatening presentations that remains undertreated.

Kyley J. Wyss, MD, FACEP, is an emergency physician with Mid-American Emergency Physicians, Springfield, IL.

Derek M. Sorensen, MD, MHPE, FACEP, is Associate Professor, Departments of Emergency Medicine and Surgery, Wright State University, Boonshoft School of Medicine, Dayton, OH.

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