Anaphylaxis

Steven Rougas, M.D., M.S.

Basic Information

Definition

Anaphylaxis is a severe allergic reaction that is rapid in onset and life-threatening. It is characterized by respiratory, cardiovascular, gastrointestinal, and cutaneous manifestations, as well as vasodilatory hemodynamic changes in response to a particular allergen. Anaphylactoid reaction is an entity closely related to anaphylaxis and is caused by release of mast cells and basophil mediators triggered by non–IgE-mediated events.

Synonyms

Anaphylactoid reaction.

ICD-10CM CODES
T78.2	Anaphylactic shock, unspecified, initial encounter
T78.00XA	Anaphylactic reaction due to unspecified food, initial encounter
T80.52XA	Anaphylactic reaction due to vaccination, initial encounter
T50.904A	Poisoning by unspecified drugs, medicaments, and biologic substances, undetermined, initial encounter
T63.94XA	Toxic effect of contact with unspecified venomous animal, undetermined, initial encounter

Epidemiology & Demographics

Incidence

The incidence of anaphylaxis in the U.S. is 50 to 2000 episodes per 100,000 persons. Lifetime prevalence is 0.05% to 2%, with a mortality rate of 1%. Anaphylaxis rates are 0.0004% for food, 0.7% to 10% for penicillin, 0.22% to 1% for contrast media, and 0.5% to 5% after insect stings. Annual mortality is 500 to 1000 persons per year in the U.S.

Physical Findings & Clinical Presentation

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Urticaria, pruritus, skin flushing, angioedema (Table E1)

TABLEE1 Dynamics of Cardiovascular Abnormalities in Anaphylactic Shock

	At Onset of Reaction	Early Stage (Minutes) with No Treatment	Prolonged Shock
Blood pressure	↓	↓↓	↓↓↓
Pulse	↑	↑	↑↑
Cardiac output	↑	↓	↓↓
PVR	↓	→↓(^∗)	→↑↓(^∗)
Intravascular volume	→↓	↓	↓↓↓

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Dyspnea, cough, wheezing, shortness of breath
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Nausea, vomiting, diarrhea, difficulty swallowing
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Hypotension, tachycardia, weakness, dizziness, malaise, vascular collapse (Table E2)

TABLEE2 Signs and Symptoms of Anaphylaxis: Frequency of Occurrence

Sign or Symptom	Percentage of Cases
Cutaneous	>90
Urticaria and angioedema	85-90
Flush	45-55
Pruritus without rash	2-5
Respiratory	40-60
Dyspnea, wheeze	45-50
Upper airway angioedema	50-60
Rhinitis	15-20
Dizziness, syncope, hypotension	30-35
Abdominal
Nausea, vomiting, diarrhea, cramping pain	25-30
Miscellaneous
Headache	5-8
Substernal pain	4-6
Seizure	1-2

Etiology

Anaphylaxis results from a sudden systematic release of histamine and other inflammatory mediators from basophils and mast cells. This causes swelling of the mucus membranes and the urticarial rash on the skin. Virtually any substance may induce anaphylaxis.

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Foods and food additives: peanuts, tree nuts, eggs, shellfish, fish, cow’s milk, fruits, soy
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Medications: antibiotics (especially penicillins), insulin, allergen extracts, opiates, vaccines, NSAIDs, contrast media, streptokinase
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Environmental exposures: bee or wasp sting, snake venom, fire ant venom
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Blood products: plasma, immunoglobulin, cryoprecipitate, whole blood
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Latex

Diagnosis

Differential Diagnosis

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Endocrine disorders (carcinoid, pheochromocytoma)
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Globus hystericus, anxiety disorder
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Systemic mastocytosis
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Pulmonary embolism, serum sickness, vasovagal reactions
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Severe asthma (the key clinical difference is the abrupt onset of symptoms in anaphylaxis versus a history of progressive worsening of symptoms)
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Septic shock or other form of vasodilatory shock
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Airway foreign body

Workup

Workup is aimed at ruling out other conditions that may mimic anaphylaxis.

Laboratory Tests

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Laboratory evaluation is generally not helpful because anaphylaxis is typically a clinical diagnosis.
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ABG analysis may be useful to help differentiate between pulmonary embolism, status asthmaticus, and foreign body aspiration.
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Elevated serum and urine histamine levels and serum tryptase levels can be useful for diagnosis of anaphylaxis, but these tests are not commonly available in the emergency setting.

Imaging Studies

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Generally not helpful.
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Chest radiography for evaluation of foreign body aspiration or pulmonary pathology is indicated in patients with acute respiratory compromise.
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Consider ECG in all patients with sudden loss of consciousness or reports of chest pain or dyspnea and in any elderly patient. ECG in anaphylaxis usually reveals sinus tachycardia.

Treatment

Nonpharmacologic Therapy

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Establish and protect airway. Provide supplemental O₂ if indicated.
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IV access should be rapidly established, and IV fluids (i.e., normal saline) should be administered.
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Cardiac monitoring is recommended.

Acute General Rx

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Epinephrine should be rapidly administered as an IM injection at a dose of 0.3 mg of aqueous epinephrine for adults and children >30 kg. Epinephrine 0.15 mg should be given for children <30 kg (1:1000 concentration). Intramuscular administration is preferred because it provides more reliable and quicker rise to effective plasma levels. The dose may be repeated after approximately 5 to 15 min if symptoms persist.
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Adjunct therapies include H₁ and H₂ receptor antagonists such as diphenhydramine 25 to 50 mg IV or IM (or PO in mild cases) and famotidine 20 to 40 mg IV (or PO in mild cases). Although useful to improve cutaneous erythema and pruritus, H₁ antagonists are not as effective as epinephrine, since onset of action is 1 to 2 hours and they are not effective in reversing upper airway obstruction or improving hypotension.
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Corticosteroids are not useful in the acute episode because of their slow onset of action; however, they should be administered in most cases to prevent prolonged or recurrent anaphylaxis. Commonly used agents are prednisone, methylprednisolone 40 to 250 mg IV in adults (1 to 2 mg/kg in children), or dexamethasone.
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Aerosolized β-agonists (e.g., albuterol, 2.5 mg, repeat prn 20 min) are useful to control bronchospasm.
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Vasopressor therapy with epinephrine (1:10,000), or dopamine is indicated in patients with refractory hypotension/cardiovascular collapse after crystalloid resuscitation.
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Table E3 summarizes drugs and other agents used in anaphylaxis therapy.

TABLEE3 Drugs and Other Agents Used in Anaphylaxis Therapy

Drug	Dose/Route of Administration	Comment
Epinephrine	Adult: 0.3-0.5 ml of 1:1000 dilution IM in the lateral thigh Child: 0.01 mg/kg or 0.1-0.3 ml of 1:1000 solution IM in the lateral thigh	Initial drug of choice for all anaphylactic episodes; should be given immediately; may repeat every 5-15 min
	0.1-1.0 ml (0.1-1.0 mg) of 1:1000 aqueous epinephrine diluted in 10 ml of normal saline IV
	Alternatively, epinephrine infusion prepared: 1 mg (1 ml) of 1:1000 dilution added to 250 ml of D5W to yield concentration of 4.0 μg/ml Solution infused at 1-4 μg/min (15-60 drops/min with microdrip [60 drops/min = 1 ml = 60 ml/h]), increasing to maximum 10 μg/min	If no response to IM administration and patient in shock with cardiovascular collapse
Antihistamines
Diphenhydramine	Adult: 25-50 mg IM or IV Child: 12.5-25 mg PO, IM, or IV	Route depends on episode severity
Cimetidine	Adult: 4 mg/kg IV	Cimetidine given slowly; rapid rate associated with hypotension Child doses not well established
Ranitidine	Adult: 1 mg/kg IV
Corticosteroids
Hydrocortisone	Adult: 100 mg to 1 g IV or IM Child: 10-100 mg IV	Exact dose not established Methylprednisolone and other corticosteroids also used Prednisone, 30-60 mg, used for milder episodes
Drugs for Resistant Bronchospasm
Aerosolized β-agonist: albuterol, metaproterenol	Dose as for asthma: 0.25-0.5 ml in 1.5-2 ml saline every 4 hours as needed	Useful for bronchospasm not responding to epinephrine
Aminophylline	Dose as for asthma	Rarely used for recalcitrant bronchospasm; β-agonist preferred
Volume Expanders
Crystalloids: normal saline, Ringer’s lactate	Adult: 1000-2000 ml rapidly Child: 30 ml/kg in first hour	Rate titrated to BP response for IV volume expander After initial infusion, further administration requires tertiary care monitoring; larger amounts may be needed in β-blocked patients
Colloids (hydroxyethyl starch)	Adult: 500 ml rapidly, followed by slow infusion
Vasopressors
Dopamine	400 mg in 500 ml D5W as IV infusion; 2-20 μg/kg/min	Dopamine probably drug of choice; rate titrated to BP response; continued infusion requires intensive care monitoring
Drugs in β-Blocked Patients
Atropine sulfate	Adult: 0.3-0.5 mg IV; may repeat every 10 min to maximum 2 mg
Glucagon	Initial dose of 1-5 mg IV, followed by infusion of 5-15 μg/min titrated to BP response	Glucagon probably drug of choice, with atropine useful only for bradycardia
Ipratropium		As alternative or added to inhaled β-blockers for wheezing
BP, Blood pressure; D5W, dextrose 5% in water; IM, intramuscularly; IV, intravenously; PO, orally.

Pearls & Considerations

Comments

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Patient education regarding the nature of the illness and preventive measures is recommended. A documented history of previous anaphylactic episodes or known triggers is the most reliable method of identifying individuals at risk.
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Prescription for a prefilled epinephrine syringe (EpiPen or EpiPen Jr.) should be given, and the patient should be instructed on the use of this emergency kit, and to carry it on his/her person at all times. School-aged children should keep an additional EpiPen at school with the appropriate staff.
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Patients should also be advised to carry or wear a MedicAlert ID describing substances that have caused anaphylaxis.
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Avoidance of radiologic contrast is also recommended in those who have had a prior reaction. However, pretreatment regimens with methylprednisolone, diphenhydramine, or n-acetylcysteine exist for those who have had contrast reactions in the past.
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Venom immunotherapy immediately after a sting is effective and recommended for up to 5 yr after the anaphylactic incident.

Ferri – Anaphylaxis