Epidemiology

The prevalence of allergic disorders, including the incidence of anaphylaxis, has been increasing worldwide in the last few decades and is a topic of intensive study.^1,2 Features of Western lifestyles, such as changes in infant diets, widespread use of antibiotics, smaller family size, and cleaner child care, are believed to reduce stimulatory antigenic exposure in an individual’s early years. This has led to an environment in which the immune system is dominated by a persistent allergy-prone system.³

Pathophysiology

The immune system protects the host by distinguishing self from nonself; it tolerates the former but attacks the latter.^8,9 Allergy, allergic diseases, and hypersensitivity reactions arise when our immune system reacts inappropriately to allergens with resultant harm to the host.^1,2,10,11 For allergic diseases to occur, predisposed individuals need to first be exposed to an allergen through a process called sensitization.

The term atopy is used to describe the propensity in affected patients to produce IgE in response to otherwise innocuous environmental allergens. Atopic patients have higher serum levels of IgE antibody and a propensity for the development of one or more atopic diseases (e.g., allergic asthma, allergic rhinoconjunctivitis, atopic dermatitis, urticaria, angioedema).

Hypersensitivity reactions are mechanistically divided into four types of reactions according to the Gell and Combs classification system (Box 106.1). The immediate hypersensitivity reaction (type I), which is mediated by IgE, serves as the classic model of the immune response to allergen. On initial exposure to allergen, T helper 2 (T_H2) cells are activated, which results in the production of an array of cytokines that exert their effects on the T cells themselves, B cells, and antigen-presenting cells. IgE is elaborated and attached to the high-affinity Fc receptor on the surface of mast cells and basophils. Fixation of allergen-specific IgE leads to a series of cellular and molecular changes that prime these cells for future exposure. On reexposure, allergen cross-links the cell-bound IgE on the surface of mast cells and basophils, thereby setting in motion a complex cascade of events that lead to the release of preformed mediators such as histamine, lipid mediators, and cytokines and subsequent activation of various inflammatory pathways. These mediators and products of secondary inflammatory pathways cause adherence and chemotaxis of inflammatory cells, increased capillary permeability, vasodilation, smooth muscle contraction, and sensory nerve stimulation. A few allergen molecules can thus cause the release of a large number of mediator molecules in a designed amplification response. Examples of type I hypersensitivity reactions include allergic rhinitis, allergic asthma, urticaria, angioedema, and anaphylaxis.

See Box 106.1, Types of Hypersensitivity, online at www.expertconsult.com.

Allergens are typically carbohydrate or protein molecules (or parts of a larger molecule) that elicit an immune response.¹⁰

The inflammation that occurs in allergy is divided into three temporal phases.¹⁰ Early-phase reactions occur within minutes of exposure and are considered immediate type I hypersensitivity reactions. Late-phase reactions typically occur within 2 to 6 hours and peak 6 to 9 hours after exposure. This response is thought to be due to newly synthesized cytokines, growth factors, and chemokines, which were released more slowly than the preformed mediators primarily responsible for the early-phase reaction. This reaction often involves airway narrowing and hypersecretion of mucus in the lungs, in addition to the erythema, warmth, and pain experienced in the skin. In some individuals there is no clinical distinction between the early and late phases. Chronic allergic inflammation is the final phase in the inflammatory process. It occurs after persistent or repetitive exposure to specific allergens and results in tissue remodeling and structural changes in affected cells. Chronic allergic inflammation can further increase epithelial injury, mucus production, and thickening of airway walls.

The majority of serious sting-related reactions are caused by insects belonging to the order Hymenoptera (yellow jackets, hornets, honeybees, wasps, and fire ants).⁵ Their venom contains histamine, dopamine, various peptides, and protein enzymes that are either vasoactive or can elicit significant allergic reactions (IgE mediated).

Presenting Signs and Symptoms

Differential Diagnosis and Medical Decision Making

Allergic Rhinitis

Box 106.2 lists other diagnostic considerations in patients with symptoms that may mimic allergic rhinitis.¹² Patients older than 20 years should be investigated for nonallergic causes (e.g., polyps). Atopic patients with severely inflamed conjunctivae, lids, and periorbital structures should raise the possibility of atopic keratoconjunctivitis (Fig. 106.1) and vernal keratoconjunctivitis (Fig. 106.2). These two types of chronic allergic conjunctivitis have the potential to cause corneal erosions and ulcers leading to vision loss and should be managed in consultation with an ophthalmologist.

Box 106.2

Causes of Rhinorrhea and Nasal Obstruction

Nonallergic Rhinitis with Eosinophilia Syndrome

Nasal smears negative for allergens but with an abundance of eosinophils

Mechanical Obstruction

Foreign body

Previous trauma involving the septum

Polyps

Adenoid disease

Infectious Rhinosinusitis

Primary or secondary bacterial, viral, or fungal infections

Vasomotor Rhinitis

Profuse, clear rhinorrhea and nasal congestion—may be triggered by environmental conditions such as cold air, odors, or changes in atmospheric pressure or by the ingestion of hot or spicy foods

Drug Induced

Includes entities such as rhinitis medicamentosa (rebound from prolonged use of topical decongestants)

May be triggered by aspirin, nonsteroidal antiinflammatory drugs, or oral contraceptive use

Systemic Disease

Wegener disease, sarcoidosis

Head trauma

Modified from Greiner AN. Allergic rhinitis: impact of the disease and considerations for management. Med Clin North Am 2006;90:17–38.

Fig. 106.1 Atopic keratoconjunctivitis.

(From Baba I. Red eye—first aid at the primary level. Community Eye Health 2005;18:70–72.)

Fig. 106.2 Vernal keratoconjunctivitis.

Notice the lumpy appearance on the conjunctivae.

(From Yorston D, Zondervan M. Red eye picture quiz. Community Eye Health 2005;18:72–78.)

Typically, no diagnostic tests need to be performed in the ED. Specific IgE serum assays such as the radioallergosorbent test (RAST), enzyme-linked immunosorbent assay (ELISA), skin prick test, and nasal smears are usually performed by allergists.

Treatment

Follow-up, Next Steps in Care, and Patient Education

Epidemiology

Urticaria (hives) is a fairly common reaction that affects approximately 20% of the population at some point in their lifetime.¹⁸ It has numerous different underlying causes and consists of several different types and subtypes. Spontaneous urticaria is broadly divided into acute (<6 weeks) and chronic (≥6 weeks) forms, with the latter representing approximately 10% to 20% of cases.

Pathophysiology

The classic wheal lesions associated with urticaria are the result of edema within the mid and upper dermal layers of the skin. Dilation of lymphatic vessels and capillary venules allows extravasation of protein-rich fluid into the surrounding tissue. This complex inflammatory process involves a variable mixture of macrophages, T cells, neutrophils, eosinophils, and mast cells.¹⁹

Presenting Signs and Symptoms

Patients with urticaria usually have hives of variable duration and location.^20,21 Urticarial lesions are pruritic, erythematous, raised rashes that blanch on palpation. The lesions are typically round or oval with serpiginous borders, but they may vary in color, size, and shape (Fig. 106.3). They may be localized or appear throughout the body, but there is a slight predilection for the trunk, hands, feet, lips, tongue, and ears. Urticaria usually starts with erythema (flare) as a result of capillary vasodilation in the superficial layer of the dermis. As the protein-rich fluid extravasates into surrounding tissue, it evolves into raised wheals and may change from red to white. A history of pruritic red rash that changes in size and shape, with extension and regression over a period of hours or days, favors the diagnosis of urticaria.

Fig. 106.3 Acute urticaria.

(Copyright 2001–03, Johns Hopkins University School of Medicine. Shahbaz Janjua: Dermatlas. Available at http://www.dermatlas.org. With permission.)

Differential Diagnosis and Medical Decision Making

The first step in narrowing the differential diagnosis of urticaria is to determine whether the urticaria is acute (<6 weeks of symptoms) or chronic (≥6 weeks of symptoms).^20,21 The differential diagnosis of urticaria is outlined in Box 106.3 and illustrated in Figure 106.4.

Fig. 106.4 Algorithm for the diagnosis and treatment of urticaria.

ASA, Acetylsalicylic acid; c/w, consistent with; NSAIDs, nonsteroidal antiinflammatory drugs.

See Box 106.3, Differential Diagnosis of Urticaria, online at www.expertconsult.com

Evaluation of acute urticaria and angioedema is based on a careful history and skin examination; little additional laboratory testing should be needed. The work-up for chronic urticaria is usually performed by an allergist in the office.

Treatment

Therapy for acute urticaria includes avoidance of the suspected causative agent and administration of H₁ antihistamines (see Fig. 106.4). The second-generation H₁ antihistamines (cetirizine, loratadine, fexofenadine, desloratadine) are currently recommended as the first-line drugs.^18,20

For urticaria judged difficult to control with antihistamines alone, prednisone can be added.²⁰ If the urticarial rash is extensive and pruritus is severe, epinephrine can be administered (0.3 to 0.5 mL of a 1 : 1000 dilution intramuscularly). It may be repeated every 1 to 2 hours as needed. Caution is advised when administering epinephrine to patients at risk for coronary heart disease (>35 years of age, other risk factors for coronary artery disease). Patients with chronic urticaria can be prescribed a nonsedating H₁ antihistamine (in higher dosages) as a temporizing measure and be referred to an allergist for further care.

Follow-up, Next Steps in Care, and Patient Education

Most patients with urticaria (acute and chronic) can be managed as outpatients. Usually, a 7-day course of a second-generation H₁ antihistamine is sufficient, although a corticosteroid (prednisone) in a tapering course is sometimes added for moderate to severe cases.

Epidemiology

Angioedema (not including hereditary angioedema [HAE]) may affect 10% to 20% of the population at some time in their lives; most chronic angioedema is idiopathic. HAE is an autosomal dominant genetic disorder with an estimated prevalence of 1 per 10,000 to 150,000 persons. The incidence of angiotensin-converting enzyme inhibitor (ACEI)-associated angioedema is approximately 0.2% to 0.7% and slightly higher in the African American population. Episodes have been reported to occur within days of initiating ACEI therapy and up to 8 years later, with an average onset of approximately 10 months. Ten percent to 25% of cases of angioedema encountered in the ED are considered to be life-threatening. African Americans are more susceptible to angioedema induced by ACEIs. Other forms of angioedema have no clear association between race and the frequency or severity of the disease. In HAE, affected women tend to have more frequent attacks and a more severe clinical course. Chronic idiopathic angioedema is more common in females than in males.

Angioedema can affect patient of all ages. For patients with HAE, the onset of symptoms is often around puberty. Idiopathic angioedema is more common in those aged 30 to 50 years than in other age groups. Patients typically experience minor swelling in childhood that may go unnoticed, with increased severity noted around puberty. However, type III HAE is found in the second decade of life or later and occurs only rarely before puberty. Five percent of adult HAE carriers are asymptomatic and identified only after their children are found to be symptomatic.

Urticaria-associated angioedema occurs in nearly 50% of children with urticaria. Because urticaria occurs in 2% to 3% of children, urticaria-associated angioedema is estimated to occur in 1% to 2% of the general population.

Pathophysiology

Angioedema (swelling) refers to vasodilation and edema in the lower dermis and subcutaneous layers of the skin.²² In the majority of cases angioedema shares a similar allergic mechanism, but in selected cases it is the result of a reaction mediated by bradykinin. Both forms of angioedema can appear similar clinically, with bradykinin-mediated angioedema typically being manifested as angioedema without urticaria. They both commonly affect the eyelids, face, lips, and tongue and can potentially cause life-threatening respiratory compromise. It is important to distinguish the two forms because bradykinin-mediated angioedema may respond better to the new classes of medications, including recombinant C1 factor, kallikrein inhibitor, or a bradykinin receptor antagonist.

Bradykinin-mediated angioedema typically falls into one of two groups, HAE or acquired angioedema (AAE). HAE was first described by William Osler in 1888. It is a rare autosomal dominant disorder with an overall incidence of 1 in 50,000.²³ Approximately 25% of cases are the result of a spontaneous mutation. HAE has three subtypes. Type I (85%) is characterized by low levels of C1 esterase inhibitor (C1 INH), type II (<15%) consists of normal but poor functioning levels of C1 INH, and type III (rare) has normal C1 INH levels and activity but probably involves another unidentified defect or gene mutation at the receptor level. Currently, bradykinin is thought to be the primary molecule responsible for angioedema in patients with HAE. Documented triggers include infection, stress, trauma, oral contraceptives, pregnancy, and menstruation.²³

AAE comprises a heterogeneous group that includes drug-induced, idiopathic, and environmental agent–related angioedema and acquired C1 INH deficiency (ACID). ACID is characterized by a lack of inheritance and low-level or nonfunctional C1 INH. Drug-induced angioedema is most commonly caused by ACEIs.²⁴ Up to 50% of those who still take an ACEI after an episode of angioedema will experience recurrent episodes. Discontinuation of the medication results in resolution of the symptoms in the majority of patients (within 24 to 48 hours). ACEIs block the degradation of kinins and thereby lead to elevated levels of bradykinin and other peptides. This results in vasodilation and tissue edema of the deeper layers of the skin, which is clinically manifested as angioedema.²⁴

Presenting Signs and Symptoms

Angioedema has a brawny appearance and occurs when extravasation of fluid occurs at the subcutaneous and deep dermal layers of the skin. Patients with angioedema experience less pruritus than urticaria and often complain of a pain or burning sensation at affected sites. Angioedema also tends to involve the face, tongue, lips, and larynx but can occur in the mucosal layer of the gastrointestinal tract and genitalia in men. Involvement of the gastrointestinal tract can cause nausea, vomiting, diarrhea, and abdominal pain.

HAE is usually manifested in the second decade of life and appears either alone or with urticaria. Recurrent angioedema without urticaria later in life (e.g., middle age) may suggest some form of AAE, including ACID- and ACEI-induced angioedema (if undergoing ACEI therapy). Both HAE and ACEI-induced angioedema tend to have a predilection for the face, tongue, lips, oropharynx, and larynx. Patients with HAE may complain of a lump or tightness in the throat and progressive dyspnea. Physical examination may reveal hoarseness, inspiratory stridor, and rarely, urticaria. Prompt attention to airway management can be lifesaving. After stabilization, these patients need to be identified and referred to an allergist for further work-up and treatment.

Differential Diagnosis and Medical Decision Making

When angioedema is suggested by the history and physical examination, it is important to determine whether it is associated with other allergic findings, urticaria, a family history, or other medications (ACEIs). The differential diagnosis of angioedema is outlined in Box 106.4.

Patients suspected of having HAE should first have their complement 4 (C4) and complement 2 (C2) levels checked. As recommended by the consulting allergist or internist, other tests can include a CH₅₀ (total complement activity) test, C1 INH test, or C1 functional assay. Additional screening tests may be considered to help rule out occult infection, hematologic or oncologic pathology, and rheumatologic or inflammatory disorders, which may aid the consultant in subsequent evaluation of these patients.

Treatment

The first priority in the management of patients with acute angioedema is to secure a patent airway if needed.^22,23 Endotracheal intubation should be considered early in patients with progressive laryngeal edema. As soon as the patient is situated, intravenous access should be established, oxygen administered, and the patient placed on a monitor.

The majority of cases of angioedema are type I hypersensitivity reactions. If signs of airway compromise or hypoxia are present, epinephrine should be administered (0.3 to 0.5 mL of a 1 : 1000 dilution intramuscularly) and repeated every 5 minutes as needed. Nebulized racemic (or regular) epinephrine (0.5 mL of a 2.25% racepinephrine solution; multiple doses are acceptable in patients without intravenous access) can be a temporizing measure for pharyngeal and laryngeal edema before or in addition to parenteral administration of epinephrine. In patients with mild symptoms and no airway involvement, H₁ and H₂ antihistamines should be used first. Parenteral steroids (methylprednisolone, 125 mg intravenously) should be administered for moderate to severe attacks.

Epinephrine, antihistamines, and corticosteroids are generally ineffective in the treatment of HAE and ACEI-induced angioedema, although they are commonly given in the acute setting. The use of new drugs for acute HAE attacks and ACEI-induced angioedema is still in the formative stage. Plasma-derived C1 INH concentrate (Berinert, 20 U/kg intravenously, Cinryze, 1000 units intravenously) is currently available in the United States.¹⁵ Ecallantide, a kallikrein inhibitor (30 mg subcutaneously in adults), is another recent agent approved by the Food and Drug Administration for the treatment of acute HAE. Aminocaproic acid, tranexamic acid, and anabolic androgens (danazol, stanozolol) are often prescribed for HAE prophylaxis but may be considered for the treatment of acute episodes. Additional treatment alternatives include solvent detergent–treated plasma or fresh frozen plasma, although these therapies are considered less safe.²³

Follow-up, Next Steps in Care, and Patient Education

Patients with mild symptoms who improved clinically after treatment and were observed for 4 to 6 hours in the ED can be discharged home with H₁ antihistamines and a short course of steroids. If the patient was taking an ACEI, its use should be stopped. Replacement candidates include calcium channel blockers and thiazides. Angiotensin receptor blockers are deemed acceptable by some authorities because the risk for angioedema from these agents is considered acceptably low.^24,25 Beta-blockers are not advised in the initial setting because of the theoretic risk of exacerbating the angioedema and potential antagonistic effects with epinephrine.

Inpatient admission is warranted for those with moderate to severe symptoms who fail to display signs of resolution after 4 to 6 hours in the ED. In particular, patients with HAE should be managed in consultation with their primary physician or allergist. Most of these patients, especially those with face and laryngeal involvement, warrant observation overnight in the hospital.

Epidemiology

Anaphylaxis is a life-threatening systemic hypersensitivity reaction that is rapid in onset and usually precipitated within minutes of exposure to an allergen. Because of lack of data the true incidence of anaphylaxis is unknown, but recent evidence suggests that it is increasing and its incidence may be as high as 2%.^26,27 Risk factors for anaphylaxis include atopy, higher socioeconomic status, northern locations, female sex (adults), and route of allergen exposure. An individual with a history of asthma is more likely to experience a severe or fatal reaction.²⁷

Pathophysiology

Anaphylaxis is commonly an IgE-mediated type I hypersensitivity reaction, but it can also occur through other immunologic mechanisms or direct mast cell activation (formerly known as an anaphylactoid reaction). The resultant degranulation of mast cells and basophils causes the release of preformed mediators such as histamine, tryptase, carboxypeptidase A₃, chymase, and tumor necrosis factor-α, as well as newly generated mediators such as leukotrienes, prostaglandins, cytokines, and platelet-activating factor. These vasoactive molecules together are believed to be responsible for the pathophysiology of anaphylaxis. Of these mediators, histamine is probably the most important. It mediates systemic vasodilation and increases vascular permeability, cardiac contractility, and glandular secretion. The leukotrienes, together with platelet-activating factor, contribute to vascular permeability and, in combination with prostaglandins (D₂), cause bronchoconstriction.

Presenting Signs and Symptoms

Anaphylaxis is a systemic reaction of rapid onset that involves multiple organ systems, principally the cutaneous, respiratory, cardiovascular, gastrointestinal, and central nervous systems (Box 106.5).³¹ Patients may initially experience warmth and tingling of the face, mouth, and chest, followed by nasal congestion, sneezing, and ocular itching and tearing. Urticaria, pruritus, and angioedema occur roughly 90% of the time.

The majority of anaphylactic reactions become clinically evident within minutes after parenteral exposure (average of 5 to 30 minutes), with a longer latent time (2 hours) after the ingestion of a triggering agent. In general, the sooner the clinical syndrome is manifested after exposure to the allergen, the more severe the reaction. Most fatalities occur within the first 30 minutes after exposure. In the setting of shock, cutaneous symptoms may be absent as a result of compensatory vasoconstriction. Anaphylaxis may precipitate an acute coronary syndrome in what is known as cardiac anaphylaxis.³² More commonly in the elderly, the initial complaint may be abdominal pain and cramping.

In approximately 20% of patients, anaphylaxis may recur 1 to 72 hours after apparent clinical resolution of all signs and symptoms in what is called a biphasic reaction.³³ There is currently no evidence or expert consensus on clinical predictors of the occurrence of a biphasic anaphylactic reaction, although it has been suggested that a biphasic reaction is rare in patients without hypotension and airway obstruction during the initial evaluation.³⁴ Most authorities recommend an observation period (8 to 24 hours) after the initial manifestation to minimize the untoward effects of the biphasic reaction.³³

Differential Diagnosis and Medical Decision Making

The clinical spectrum of anaphylaxis overlaps that of several other syndromes, especially those involving the skin and cardiorespiratory system (Box 106.6). Vasovagal reactions may mimic early anaphylaxis, although these patients usually have bradycardia, hypotension, diaphoresis, and pallor, as opposed to the tachycardia, hypotension, diaphoresis, and urticaria usually associated with anaphylaxis. Anaphylactic shock may also appear clinically indistinguishable from other forms of shock (distributive, septic, or cardiogenic). The acute onset and characteristic angioedematous urticarial rash favor the diagnosis of anaphylactic shock. Flushing syndromes also frequently mimic anaphylactic reactions. They may be associated with dry skin or diaphoresis and are the result of numerous different drugs, ingestants, and other physiologic syndromes.

Anaphylaxis is diagnosed clinically. The diagnosis is considered highly likely when any of three clinical criteria in Box 106.7 are met.³⁵

Currently, histamine and tryptase are the only measurable markers of anaphylaxis in clinical laboratories.³¹ Histamine plasma levels become elevated approximately 10 minutes after the onset of symptoms and remain so for up to an hour. Peak levels of serum tryptase occur between 60 and 90 minutes and persist for as long as 6 hours. These markers must be determined within the time frames mentioned and may be helpful when it is uncertain whether anaphylaxis has occurred. It should be noted that food-induced anaphylaxis may not be accompanied by elevated levels of tryptase. Additional laboratory tests and imaging may be necessary to help rule out other disease processes.

Treatment

Early administration of epinephrine is the mainstay of treatment of anaphylaxis (Box 106.8). It should be administered quickly and preferably intramuscularly in the lateral aspect of the thigh (vastus lateralis). Epinephrine should be considered if anaphylaxis is suspected even when only one system (e.g., skin) is involved. Doses can be repeated every 5 to 10 minutes or more frequently as indicated clinically.^27,31 Caution should be exercised in patients with risk factors for ischemic heart disease, although there are no absolute contraindications to epinephrine in those initially seen in anaphylactic shock. Intravenous infusion should be used only in patients who remain hypotensive and have failed to respond to multiple intramuscular injections.^27,31 Inhaled epinephrine may be used as adjunctive therapy for laryngeal edema but should never replace the intramuscular or intravenous route (Fig. 106.5).

Fig. 106.5 Treatment algorithm for possible anaphylaxis (see Box 106.8 for drug dosages and indications).

CXR, Chest radiograph; ECG, electrocardiogram; ED, emergency department; gtt, drops; ICU, intensive care unit; IM, intramuscularly; IV, intravenous; NS, normal saline; SQ, subcutaneously.

In conjunction with the administration of epinephrine, the patient should be placed in the supine position with the lower extremities elevated. Intravenous access should be established, supplemental oxygen administered, and the patient placed on a monitor. Patients with rapidly progressive respiratory insufficiency will benefit from early endotracheal intubation. Use of rapid-sequence intubation should be approached with great caution because of the potential for rapid deterioration of the oral and laryngeal edema. Plans for backup airway support and rescue airway devices, including a surgical airway, may be prudent.

Hypotension is treated aggressively with crystalloid infusion and colloid as indicated clinically. Caution should be taken in patients with a history of congestive heart failure. Patients with persistent hypotension despite appropriate doses of epinephrine and intravenous fluid resuscitation should be administered vasopressors drips (see Box 106.8).

H₁ antihistamine (diphenhydramine) should be given to improve the itching and hives in patients with anaphylaxis. H₂ antihistamines (ranitidine, cimetidine) have a synergistic effect with H₁ antihistamines and should be given because they improve vascular permeability, flushing, gastric secretion, and mucus production in the airway. Antihistamines, however, should be considered second-line agents after epinephrine. Inhaled β-agonists (albuterol) can be administered for bronchospasm refractory to appropriate doses of epinephrine. Glucocorticosteroid provides no immediate benefit in the acute treatment of anaphylaxis, although it may be helpful in preventing biphasic reactions.

Special Considerations

Follow-up, Next Steps in Care, and Patient Education

Patients who experience complete resolution of symptoms and were never hypotensive can potentially be discharged home. Although the time frame for biphasic reactions varies significantly, limited literature suggests that patients be observed in the ED for up to 8 hours.³³ Oral H₁ antihistamines such as diphenhydramine (50 mg every 6 hours for 72 hours) and H₂ blockers such as ranitidine (150 mg every 12 hours for 72 hours) along with oral prednisone may prevent possible relapse.³⁷ These patients should be instructed to return to the ED if they experience any recurrent symptoms consistent with their previous anaphylactic reaction.

All patients who have experienced an anaphylactic or significant allergic reaction should be prescribed at least two Epi-Pens, one kept at the common residence and another in the purse or briefcase. In addition, patients should be taught how to self-administer it. Predisposed patients should be encouraged to wear a Medic-Alert bracelet or carry a wallet card identifying their hypersensitivity. Patients should also be referred to an allergist for possible skin testing and hyposensitization immunotherapy.

Hospital admission should be considered for patients who show slow clinical improvement, were hypotensive, and had upper airway involvement or persistent bronchospasm. Patients at risk for a biphasic reaction, such as those maintained on chronic beta-blocker therapy, may also be candidates for extended observation in the hospital.