AUTHOR INFORMATION

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Authored by Jeffrey F Linzer, Sr, MD, MICP, FAAP, FACEP, Assistant Professor of Pediatrics and Emergency Medicine, Emory University School of Medicine; Associate Medical Director, Compliance and Business Affairs, Div of Pediatric Emergency Medicine, Department of Pediatrics, Children's Healthcare of Atlanta at Egleston

Jeffrey F Linzer, Sr, MD, MICP, FAAP, FACEP, is a member of the following medical societies: American Academy of Pediatrics, American College of Allergy, Asthma and Immunology, and American College of Emergency Physicians

Edited by Kirsten Bechtel, MD, Assistant Professor, Department of Pediatrics, Division of Pediatric Emergency Medicine, Yale-New Haven Children's Hospital; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc; Wayne Wolfram, MD, MPH, Clinical Associate Professor, Departments of Pediatrics, Children's Hospital and University of Cincinnati; John Halamka, MD, Chief Information Officer, CareGroup Healthcare System, Assistant Professor of Medicine, Department of Emergency Medicine, Beth Israel Deaconess Medical Center; Assistant Professor of Medicine, Harvard Medical School; and Richard G Bachur, MD, Assistant Professor of Pediatrics, Harvard Medical School; Associate Chief and Fellowship Director, Division of Emergency Medicine, Children's Hospital of Boston

Author's Email:	Jeffrey F Linzer, Sr, MD, MICP, FAAP, FACEP
Editor's Email:	Kirsten Bechtel, MD

eMedicine Journal, February 9 2006, VOLUME 7, Number 2

INTRODUCTION

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Background: Anaphylaxis is an acute, potentially life-threatening syndrome, with multisystem manifestations resulting from the rapid release of inflammatory mediators.

Originally defined as a potentially fatal immunoglobulin E (IgE)-mediated response to antisera, the same clinical presentation is encountered with non-IgE reactions. Instead of using separate terminology that is based on whether the underlying mechanism is IgE mediated or not (anaphylaxis versus anaphylactoid), the term anaphylaxis syndrome is used to describe the clinical event.

In children, foods can be a very significant trigger for IgE-mediated anaphylaxis. Milk, egg, wheat, and soy (MEWS) as a group are the most common food allergens; however, peanuts and fish are among the most potent. Children can develop anaphylaxis from the fumes of cooking fish or residual peanut in a candy bar.

Other common triggers include preservatives (in food and drugs), medications (antibiotics), insect venom (bee sting) and bioactive substances (eg, blood, blood products). Environmental allergens such as pollens, molds, and dust mites are a less common and infrequent cause of anaphylaxis.

Non-IgE triggers include infection, opiates, radiocontrast dye, and exercise.

Pathophysiology: Activation of mast cells and basophils results in the release of several inflammatory and vasoactive substances such as histamine, prostaglandins, leukotrienes, tryptase, and platelet activating factor. In anaphylaxis, these substances most commonly involve the skin, respiratory, cardiovascular, and gastrointestinal systems. As a result, urticaria, angioedema, bronchospasm, bronchorrhea, laryngospasm, increased vascular permeability and decreased vascular tone, and bloody diarrhea can develop.

The most common form of anaphylaxis is due to an IgE-mediated reaction. A previously sensitized B lymphocyte produces IgE against a specific antigen. The IgE resides on the mast cells and basophils. When the specific antigen, or one similar to it, encounters the immunoglobulin, mast cell and basophil degranulation occurs and inflammatory and vasoactive substances are released.

Release of inflammatory and vasoactive substances can occur through several non–IgE-mediated mechanisms as follows:

• Activation by other immunoglobulins (eg, IgG) (infection)

• Stimulation of the complement cascade to produce C3a, C4a, and C5a anaphylatoxin (antigen-antibody)

• Direct action on mast cells and basophils (opiates, radiocontrast media)

• Idiopathic or unknown cause

Frequency:

• In the US: Frequency of this syndrome is difficult to determine because it often is mistaken for other disease processes. The prevalence of nonfatal cases of anaphylaxis ranges from 0.7-10%. Approximately 1:7,500,000 fatal anaphylactic reactions to penicillin occur per year.

• Internationally: Prevalence is similar to that in the US.

Mortality/Morbidity: Risk of death due to respiratory and cardiovascular complications is significant. Mortality rate estimates vary from 100 to more than 500 cases per year in the US.

Race: While asthma is more prevalent and has a higher mortality rate in African American children, no data exist to suggest that the same risk applies to anaphylaxis.

Sex: Unknown

Age: Unknown

CLINICAL

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History: Anaphylaxis is a range of signs and symptoms from hives and wheezing to cardiovascular collapse and death. At least 2 organ systems (most commonly skin, respiratory, cardiovascular, gastrointestinal systems) need be involved to make the diagnosis.

• Often a history of exposure to a known trigger is given, (eg, bee sting, peanut ingestion, antibiotic administration). At times, the inciting agent may be unknown or unclear.

• Symptoms may develop slowly and insidiously over several hours or may rapidly progress over several minutes. Parenteral agents generally have a faster onset of symptoms than ingested ones.

• Children may not be able to express the initial symptoms of anaphylaxis. They may initially have apparent discomfort or a generalized irritability. Additionally, the child may not be able to identify the triggering agent (eg, food) even when known to the parent or caretaker.

Physical: Initial symptoms may include an awareness that "something isn't right," a tingling sensation in the mouth, itchy watery nose and eyes, and/or the feeling of being warm and flushed.

• Cutaneous (skin)

• Urticaria (hives, welts, "whelps")

• Angioedema (swelling) of the face and/or extremities

• Respiratory

• Cough

• Wheezing

• Hoarseness

• Chest pain

• Stridor

• Gastrointestinal

• Throat tightness

• Nausea/vomiting

• Abdominal cramps

• Diarrhea (at times bloody)

• Cardiovascular

• Tachycardia (rapid heart rate)

• Arrhythmias (irregular heart beat)

• Decreased peripheral perfusion

• Hypotension (usually late finding in children in uncompensated shock)

• Central nervous system
  • Dizziness

  • Syncope (fainting)

  • Altered mental status

  • Coma

Causes: The following is only meant to be illustrative of the more common triggers but should not be considered an exhaustive listing. These triggering agents may cause an IgE or non-IgE mediated anaphylaxis.

• Foods - MEWS, fish, shell fish, legumes (peanuts), nuts

• Medicinals - Antibiotics (penicillins, cephalosporins), local anesthetics (lidocaine), analgesics (aspirin, nonsteroidal anti-inflammatories [ibuprofen], opiates), radiocontrast media

• Biologicals - Insect venom (bee sting, ant bite), blood and blood products, allergen extracts

• Preservatives and additives - Metabisulfite, monosodium glutamate

• Other - Latex, unknown/idiopathic

DIFFERENTIALS

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Angioedema
Asthma
Bee and Hymenoptera Stings
Serum Sickness
Shock, Cardiogenic
Shock, Hypovolemic

Other Problems to be Considered:

Physical urticaria
Syncope

WORKUP

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Lab Studies:

• Anaphylaxis is essentially a clinical diagnosis. Laboratory tests are not useful for the acute diagnosis of this condition. Tryptase has been used to distinguish anaphylactic reactions from nonallergic conditions.

Other Tests:

• Radioallergosorbent test (RAST) or cutaneous antigen testing (preferably by a specialist) can be used after recovery to try to identify the inciting antigen.

TREATMENT

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Prehospital Care: Prehospital care should be directed at stabilization of the airway, breathing, and circulation.

• A nasopharyngeal airway is better tolerated in the responsive child than an oropharyngeal airway. An advanced airway (eg, endotracheal intubation) should be placed if the patient has decreased oxygen saturation and/or decreasing level of consciousness.

• High-flow oxygen

• Intravenous access

• Epinephrine is the drug of choice and is a physiologic antagonist of histamine. Early use can relieve symptoms.

• Nebulized albuterol for cough and wheezing

Emergency Department Care: Primary attention is directed at the ABCs. If not already given, the physiologic antagonist epinephrine should be used as soon as the diagnosis is suspected. While some debate is present in the literature, H1 and H2 histamine antagonists should be used. Evidence exists that stimulation of both receptors may rarely lead to vasodilation and dysrhythmias. H1 and H2 blockers tend to be more effective at ameliorating skin findings.

Not all patients will present in shock. In fact, most patients will have only 2-3 organ systems involved. Therapy is directed towards reversing the effects of released inflammatory mediators and preventing ongoing reactions.

• An advanced airway (eg, endotracheal intubation) should be placed if patient's oxygen saturation cannot be maintained and/or if the level of consciousness is decreasing.

• High-flow 100% oxygen (warm, humidified preferred) by face mask

• Epinephrine, 1:1000 (ie, 1 mg/mL) SC, is the initial drug of choice. It may be repeated every 20 minutes, not to exceed 3 doses. Some authorities feel that the IM route may be more effective than SC when peripheral perfusion is poor. Epinephrine, 1:10,000 IV/IO, is used when the patient has significant poor peripheral perfusion, eg, shock.

• Children younger than 6 years who are in extremis: Intraosseous access is indicated if an IV cannot be established in 3 tries or in 90 seconds.

• A fluid bolus of lactated Ringer solution or isotonic sodium chloride solution (20 mL/kg) should be used for initial cardiovascular support. Repeat boluses up to 60-100 mL/kg may be necessary for correcting the hypovolemia.

• If cardiac output is ineffective despite IV fluids or if hypotensive, start an epinephrine drip after placing the patient in Trendelenburg position.

• Norepinephrine or dopamine can also be used to support blood pressure.

• Antihistamines

• The H1 blocker hydroxyzine is a better anti-urticarial agent than diphenhydramine but must be used with caution when given IV.

• Ranitidine and cimetidine are acceptable H2 antagonists with a low incidence of adverse effects.

• Nebulized albuterol, given either at 20-minute intervals or continuously, should be used to reverse bronchospasm. Giving ipratropium with albuterol may provide additional bronchodilation. Nebulized epinephrine can be used for stridor secondary to laryngeal edema.

• Corticosteroids do not have an immediate effect on the symptoms but are useful in reducing or eliminating the biphasic "late phase" reaction.

• Patients with a history of mild symptoms that have resolved prior to arrival to the ED may be discharged after a short observation period (2-4 h).

• Those with more moderate symptoms and/or a significant history of atopy (eg, asthma, allergic rhinitis) are at risk for a late phase reaction.

• Observation for 12-24 hours is warranted in these cases.

Consultations: Patients with anaphylaxis should follow up with their pediatrician for allergy evaluation and counseling. Some patients with severe atopy, uncertain allergic triggers, or repeated anaphylaxis require referral to an allergist.

MEDICATION

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Adrenergic agonists (epinephrine) and antihistamines (H1 and H2 blockers) are most important to management of this condition. Other important agents are discussed but not always necessary.

Drug Category: Adrenergic agonists -- These agents stimulate different adrenergic receptors. Effectiveness in treating anaphylaxis depends on which receptor types are stimulated and on the concentration of receptors in the target tissues.

Drug Name	Epinephrine (Adrenaline, EpiPen, Bronitin) -- DOC for treating anaphylaxis. Elicits alpha-agonist effects that include increased peripheral vascular resistance, reversed peripheral vasodilatation, systemic hypotension, and vascular permeability. Beta-agonist effects of epinephrine include bronchodilatation, chronotropic cardiac activity, and positive inotropic effects.
Pediatric Dose	Initial treatment: 0.01 mg/kg/dose (0.01 mL/kg/dose 1:1000) SC/IM q20min up to 3 doses (dose range 0.1-0.5 mg/dose) - half of initial SC dose may be injected around any obvious injection site (eg, bee sting); 0.1 mL/kg/dose 1:10,000 IV/IO should be considered if patient has significant hypoperfusion (not to exceed 1 mg) Auto-injectors (EpiPen): <30 kg: EpiPen Jr (1:2000) SC delivers 0.15 mg/dose >30 kg: EpiPen (1:1000) SC delivers 0.3 mg/dose Continuous IV infusion: 0.1-1 mcg/kg/min IV/IO, titrated to effect
Contraindications	Documented hypersensitivity; cardiac arrhythmias or angle-closure glaucoma; local anesthesia in areas such as fingers or toes because vasoconstriction may produce sloughing of tissue; do not use during labor (may delay second stage of labor)
Interactions	Increases toxicity of beta-blocking and alpha-blocking agents and of halogenated inhalational anesthetics; TCAs enhance pressor response
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in elderly patients, prostatic hypertrophy, hypertension, cardiovascular disease, diabetes mellitus, hyperthyroidism, and cerebrovascular insufficiency; rapid IV infusions may cause death from cerebrovascular hemorrhage or cardiac arrhythmias

Drug Name	Dopamine (Intropin) -- Stimulates both adrenergic and dopaminergic receptors. Hemodynamic effect is dependent on the dose. Lower doses ( <5 mcg/kg/min) predominantly stimulate dopaminergic receptors that in turn produce renal and mesenteric vasodilation. Cardiac stimulation and renal vasodilation produced by higher doses.
Pediatric Dose	1-5 mcg/kg/min IV; not to exceed 50 mcg/kg/min
Contraindications	Documented hypersensitivity; pheochromocytoma, ventricular fibrillation
Interactions	MAO inhibitors may prolong effects of dopamine; beta-adrenergic blockers may antagonize peripheral vasoconstriction caused by high doses of dopamine; butyrophenones (eg, haloperidol) and phenothiazines can suppress dopaminergic renal and mesenteric vasodilation induced with low-dose dopamine infusion; concurrent administration of diuretic agents with low-dose dopamine may produce additive effects on urine flow; hypotension and bradycardia may occur with phenytoin; dopamine may decrease effects of phenytoin
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Closely monitor urine flow, cardiac output, pulmonary wedge pressure, and blood pressure during the infusion; prior to infusion, correct hypovolemia with either whole blood or plasma, as indicated; monitoring central venous pressure or left ventricular filling pressure may be helpful in detecting and treating hypovolemia

Drug Name	Dobutamine (Dobutrex) -- Produces vasodilation and increases inotropic state. At higher doses may cause increased heart rate, exacerbating myocardial ischemia. Major indication is blood pressure support in patients with cardiac dysfunction.
Pediatric Dose	5-20 mcg/kg/min IV, titrate to effect
Contraindications	Documented hypersensitivity; idiopathic hypertrophic subaortic stenosis, atrial fibrillation or flutter
Interactions	Beta-adrenergic blockers antagonize effects of dobutamine; general anesthetics may increase toxicity
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Dobutamine should not be used in patients with hypovolemia; hypovolemic state should be corrected before using this drug

Drug Name	Isoproterenol (Isuprel) -- Has beta-1 and beta-2 adrenergic receptor activity. Binds beta-receptors of heart, smooth muscle of bronchi, skeletal muscle, vasculature, and alimentary tract. Has positive inotropic and chronotropic actions. Used if patient is taking beta-blockers.
Pediatric Dose	0.05-2 mcg/kg/min IV/IO, titrate to effect
Contraindications	Documented hypersensitivity; tachyarrhythmias, tachycardia or heart block caused by digitalis intoxication, ventricular arrhythmias that require inotropic therapy, angina pectoris
Interactions	Bretylium increases action of vasopressors on adrenergic receptors which may in turn result in arrhythmias; guanethidine may increase effect of direct-acting vasopressors, possibly resulting in severe hypertension; TCAs may potentiate pressor response of direct-acting vasopressors
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	By increasing myocardial oxygen requirements while decreasing effective coronary perfusion, isoproterenol may have deleterious effect on injured/failing heart; in organic disease of AV node and its branches, may paradoxically worsen heart blocks or precipitate Adams-Stokes attacks; caution in coronary artery disease, coronary insufficiency, diabetes, hyperthyroidism, and sensitivity to sympathomimetic amines; if heart rate exceeds 110 beats/min, may be advisable to decrease infusion rate or temporarily discontinue infusion

Drug Category: Antihistamines -- Decrease histamine activity by reversible competitive blockade of the histamine receptor. H1-receptor stimulation can lead to bronchial smooth muscle constriction and capillary leakage. H2-receptor activity increases gastric acid secretion and pacemaker rate. Stimulation of histamine H1 and H2 receptors may produce vasodilation and dysrhythmias. Therefore, use of H1 and H2 blockers should be considered.

Drug Name	Hydroxyzine (Atarax) -- Antagonizes H1 receptors in periphery. May suppress histamine activity in subcortical region of CNS. DOC, but is limited by its route of administration.
Pediatric Dose	0.5-1 mg/kg/dose PO/IM q6h prn
Contraindications	Documented hypersensitivity; SC, IV, or intra-arterial administration
Interactions	CNS depression may increase with alcohol or other CNS depressants
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	IV and SC administrations associated with thrombosis and digital gangrene though has been given slowly IV through central lines without problems; associated with clinical exacerbations of porphyria (may not be safe for porphyric patients); ECG abnormalities (alterations in T waves) may occur; may cause drowsiness

Drug Name	Diphenhydramine (Benadryl) -- Competes with histamine for H1-receptor sites in GI tract, blood vessels, and respiratory tract. Preferred agent when IV antihistamine is required.
Pediatric Dose	1 mg/kg/dose PO/IV/IM/IO q6h prn, not to exceed 300 mg/d
Contraindications	Documented hypersensitivity; use with MAOIs
Interactions	Potentiates effect of CNS depressants; because of alcohol content, do not give syrup dosage form to patient taking medications that can cause disulfiramlike reactions
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	May cause paradoxical excitation; may exacerbate angle-closure glaucoma, hyperthyroidism, peptic ulcer, and urinary tract obstruction

Drug Name	Ranitidine (Zantac) -- H2 antagonist (DOC) which, when combined with an H1 type, may be useful in treating allergic reactions that do not respond to H1 antagonists alone.
Pediatric Dose	0.75-1.5 mg/kg/dose PO/IV/IM/IO q6-8h, not to exceed 300 mg/d; higher doses are used for hypersecretory conditions
Contraindications	Documented hypersensitivity
Interactions	May decrease effects of ketoconazole and itraconazole; may alter serum levels of ferrous sulfate, diazepam, nondepolarizing muscle relaxants, and oxaprozin
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Caution in renal or liver impairment; if changes in renal function occur during therapy, consider adjusting dose or discontinuing treatment

Drug Name	Cimetidine (Tagamet) -- If no response to H1 antagonist alone, coadministration with this H2 antagonist treats itching and flushing in anaphylaxis, pruritus, urticaria, and contact dermatitis.
Pediatric Dose	10 mg/kg/dose PO/IV/IM/IO q6h
Contraindications	Documented hypersensitivity
Interactions	Can increase blood levels of theophylline, warfarin, tricyclic antidepressants, phenytoin, quinidine, propranolol, metronidazole, procainamide, and lidocaine
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Elderly patients may experience confusional states; may cause impotence and gynecomastia in young males; may increase levels of many drugs; adjust dose or discontinue treatment if changes in renal function occur

Drug Category: Bronchodilators -- Provide relief of bronchial smooth muscle contraction.

Drug Name	Albuterol (Ventolin, Proventil) -- DOC that relaxes bronchial smooth muscle and may decrease mediator release from mast cells and basophils. May inhibit airway microvascular leakage.
Pediatric Dose	<2 years: Not established >2 years: 0.15 mg/kg/dose nebulized in 2 mL of NS delivered q20min; 0.5 mg/kg/h continuous nebulization; not to exceed 15 mg/h Some authorities recommend for intermittent nebulizations 2.5 mg for patients <15 kg, 5 mg for patients >15 kg; continuous doses up to 2-3 mg/kg/h have been safely administered
Contraindications	Documented hypersensitivity
Interactions	Beta-adrenergic blockers antagonize effects; inhaled ipratropium may increase duration of bronchodilatation by albuterol; cardiovascular effects may increase with MAOIs, inhaled anesthetics, TCAs, and sympathomimetic agents
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in hyperthyroidism, diabetes mellitus, hypokalemia, muscle tremors, and cardiovascular disorders

Drug Name	Terbutaline (Brethine) -- Acts directly on beta2-receptors to relax bronchial smooth muscle, relieving bronchospasm and reducing airway resistance.
Pediatric Dose	Unlabeled use: 0.01-0.03 mg/kg/dose nebulized q4-6h
Contraindications	Documented hypersensitivity; tachycardia resulting from cardiac arrhythmias
Interactions	Concomitant use with beta-blockers may inhibit bronchodilating, cardiac, and vasodilating effects of beta-agonists; concomitant administration of MAOIs with beta-sympathomimetics may result in severe hypertension, headache, and hyperpyrexia, which may result in a hypertensive crisis; MAOIs may potentiate activity of beta-adrenergic agonists on the vascular system; concurrent administration of oxytocic drugs such as ergonovine with terbutaline may result in severe hypotension
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Through intracellular shunting, terbutaline may decrease serum potassium levels, which can produce adverse cardiovascular effects; decrease is usually transient and may not require supplementation; caution in diabetes mellitus

Drug Category: Corticosteroids -- Anti-inflammatory activity counters actions caused by histamine and other inflammatory mediators. Also potentiates the effect of beta-agonists.

Drug Name	Prednisone (Deltasone, Sterapred, Orasone) -- May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Blocks the release of inflammatory mediators by inhibition of phospholipase A2.
Pediatric Dose	Initial dose: 1-2 mg/kg/d PO qd or divided bid for 3-7 d, not to exceed 80 mg/d; patients with recent corticosteroid use (ie, use within the previous 60 d) may require a longer tapering regimen over 7-14 d
Contraindications	Documented hypersensitivity; viral infection, peptic ulcer disease, hepatic dysfunction, connective tissue infections, fungal or tubercular skin infections; GI bleeding or ulceration
Interactions	Coadministration with estrogens may decrease prednisone clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Caution in varicella, measles, and diabetes mellitus; abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use

Drug Name	Dexamethasone (Decadron) -- Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reducing capillary permeability. Blocks release of inflammatory mediators by inhibition of phospholipase A2. Alternative (IM) if IV/IO access is unavailable or if patient cannot tolerate PO.
Pediatric Dose	0.3-0.6 mg/kg IV/IM, not to exceed 10 mg (IO administration not ideal but possible in emergency)
Contraindications	Documented hypersensitivity; active bacterial or fungal infection
Interactions	Effects decrease with coadministration of barbiturates, phenytoin, and rifampin; dexamethasone decreases effect of salicylates and vaccines used for immunization
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Increases risk of multiple complications, including severe infections; monitor adrenal insufficiency when tapering drug; abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections are possible complications of glucocorticoid use

Drug Name	Methylprednisolone (Medrol) -- Steroids ameliorate delayed effects of anaphylactoid reactions and may limit biphasic anaphylaxis.
Pediatric Dose	1-2 mg/kg/dose PO/IV/IO q6-12h Not recommended for IM administration by some authorities because of prolonged uptake time
Contraindications	Documented hypersensitivity; viral, fungal, or tubercular skin infections
Interactions	Coadministration with digoxin may increase digitalis toxicity secondary to hypokalemia; estrogens may increase levels of methylprednisolone; phenobarbital, phenytoin, and rifampin may decrease levels of methylprednisolone (adjust dose); monitor patients for hypokalemia when taking medication concurrently with diuretics; grapefruit juice increases prednisolone concentrations; methylprednisolone and cyclosporine mutually inhibit one another resulting in increased plasma levels of each drug
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Hyperglycemia, edema, osteonecrosis, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, growth suppression, myopathy, and infections are possible complications of glucocorticoid use

FOLLOW-UP

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Further Inpatient Care:

• Patients with mild or limited symptoms that have resolved prior to arrival in the ED may be observed for a short period (2-4 h). Those with moderate symptoms and/or significant history of atopy should be observed for 12-24 hours for signs of late phase reaction (a return of symptoms).

In/Out Patient Meds:

• Patients should be continued on H1 and H2 blockers for 24-48 hours after resolution of symptoms.

• A short course of oral steroids may be warranted.

• Any patient with life-threatening symptoms should be discharged home with an epinephrine auto-injector (eg, Epi-Pen).

Transfer:

• Patients requiring aggressive or extensive stabilization should be admitted to an intensive care unit at a tertiary pediatric center.

Deterrence/Prevention:

• Exposure to inciting agent, if known, should be avoided.

• When avoidance is impossible, the patient should receive prophylaxis with H1 and H2 antihistamines and steroids after exposure. Also, the patient should have an auto-injector of epinephrine readily available for use if severe symptoms develop.

Complications:

• Respiratory failure

• Shock

• Multiorgan system failure

• Disseminated intravascular coagulation

Prognosis:

• Prognosis is good if treated early.

• Development of shock is a poor prognostic indicator.

Patient Education:

• Education about exposure risk, early management, and access to medical care

• For excellent patient education resources, visit eMedicine's Allergy Center and Allergic Reaction and Anaphylactic Shock Center. Also, see eMedicine's patient education articles Severe Allergic Reaction (Anaphylactic Shock), Food Allergy, and Allergy: Insect Sting.

MISCELLANEOUS

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Medical/Legal Pitfalls:

• Incomplete search for likely causes with subsequent failure of avoidance

• Failure to prescribe an auto-injector of epinephrine

• Failure to identify and treat appropriately

• Nonreferral to an allergy-immunology specialist (severe cases)

TEST QUESTIONS

Section 10 of 11

CME Question 1: A 3-year-old boy presents with sudden onset of facial edema and bloody diarrhea. The mother states he has never had a problem like this before. The only thing that she remembers the child having eaten before the onset of symptoms was some chocolate; however, he has eaten chocolate before without problems. Which of the following would be the physician's first therapeutic intervention?

A: Diphenhydramine
B: Epinephrine
C: Air contrast enema
D: Methylprednisolone
E: Bolus of normal saline

The correct answer is B: This child is having an allergic reaction presenting as anaphylaxis. Multisystem involvement is present (skin, cardiovascular, GI). The most likely antigen in this case would be peanuts in the chocolate. While chocolate is a less common allergen, the peanut is both common and extremely potent. Peanuts may have been in the chocolate or may have been left over from a previous product made on the same production line. As a physiologic antagonist to histamine, epinephrine is the drug of first choice.

CME Question 2: A 6-year-old boy with a history of reactive airway disease (RAD) presents with urticaria and wheezing after playing with some cats. He is clinically stable 2 hours after requiring epinephrine, hydroxyzine, ranitidine, prednisolone, and 2 albuterol nebulizer treatments. Which of the following is the next best course of action?

A: Administer an additional albuterol nebulizer treatment, then discharge the patient.
B: Observe the patient an additional 2 hours in the ED.
C: Discharge the patient with an auto-injector of epinephrine and a referral to a pediatric allergist.
D: Admit the child for 23-hour observation.
E: Discharge the child albuterol nebulizer treatments every 4 hours for the next day and a 3-day course of hydroxyzine, ranitidine, and prednisolone.

The correct answer is D: The child should be admitted for a 23-hour observation. Because of his atopic history (RAD = asthma) this child is at risk for a late phase reaction. If this would occur, early aggressive intervention would decrease the risk of morbidity and mortality. It is better to observe for late phase reaction in the hospital than to send the child home.

Pearl Question 1 (T/F): Milk, egg, wheat, and soy as a group are the most common food allergens in children.

The correct answer is True: In children, foods can be a very significant trigger for IgE-mediated anaphylaxis. Milk, egg, wheat, and soy as a group are the most common food allergens; however, peanuts and fish are among the most potent. The following is a helpful memory tool for this group of foods. Cats can cause allergies in children and cats say `MEW.` MEWS is an acronym for the 4 most common food allergies in children (milk, egg, wheat, soy).

Pearl Question 2 (T/F): A patient must be in shock before a diagnosis of anaphylaxis can be made.

The correct answer is False: The condition is a syndrome that affects multiple systems and presents as a continuum of signs and symptoms.

Pearl Question 3 (T/F): All children with anaphylaxis should be referred to a pediatric allergist.

The correct answer is False: Every child needs follow-up with their pediatrician. For clear cases with a known offending agent, counseling about emergency care is required. Some patients require referral to an allergist. Patients who have persistent, recurrent allergic symptoms and those with recurrent anaphylaxis should be referred to an allergist. A pediatric allergist is the best specialist to determine an offending agent, especially if skin testing is required. Radioallergosorbent test (RAST) alone may not be sensitive enough to identify the offending allergen.

Pearl Question 4 (T/F): An epinephrine auto-injector is the most important prescription to give a parent if discharging their child home after mild anaphylaxis.

The correct answer is True: While diphenhydramine or steroids may be continued for a few days after such an episode, the epinephrine auto-injector can be life-saving treatment, particularly because a reoccurrence of anaphylaxis can be more severe than the initial presentation. Discharging the patient with an auto-injector in hand (and after teaching how to use it) is ideal.

BIBLIOGRAPHY

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• Kemp SF, Lockey RF, Wolf BL, et al: Anaphylaxis. A review of 266 cases. Arch Intern Med 1995 Sep 11; 155(16): 1749-54[Medline].
• Lee JM, Greenes DS: Biphasic anaphylactic reactions in pediatrics. Pediatrics 2000 Oct; 106(4): 762-6[Medline].
• Liberman PL: Specific and idiopathic anaphylaxis: pathophysiology and treatment. In: Bierman CW, ed. Allergy, Asthma and Immunology from Infancy to Adulthood. 3rd ed. 1996:297-319.
• Lieberman P: The use of antihistamines in the prevention and treatment of anaphylaxis and anaphylactoid reactions. J Allergy Clin Immunol 1990 Oct; 86(4 Pt 2): 684-6[Medline].
• Lorenz W, Doenicke A, Schoning B, et al: H1 + H2-receptor antagonists for premedication in anaesthesia and surgery: a critical view based on randomized clinical trials with Haemaccel and various antiallergic drugs. Agents Actions 1980 Apr; 10(1 Pt 2): 114-24[Medline].
• Marquardt DL, Wasserman SI: Anaphylaxis. In: Middleton Jr E, ed. Allergy: Principles and Practice. 4th ed. 1993:1525-36.
• Metcalf DD: Acute anaphylaxis and urticaria in children and adults. In: Schocket AL, ed. Clinical Management of Urticaria and Anaphylaxis. 1992:70-96.
• Sicherer SH, Forman JA, Noone SA: Use assessment of self-administered epinephrine among food-allergic children and pediatricians. Pediatrics 2000 Feb; 105(2): 359-62[Medline].

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