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By Peter J. Delves, PhD

Anaphylaxis is an acute, potentially life-threatening, IgE-mediated allergic reaction that occurs in previously sensitized people when they are reexposed to the sensitizing antigen. Symptoms can include stridor, dyspnea, wheezing, and hypotension. Diagnosis is clinical. Treatment is with epinephrine. Bronchospasm and upper airway edema may require inhaled or injected β-agonists and sometimes endotracheal intubation. Persistent hypotension requires IV fluids and sometimes vasopressors.


Anaphylaxis is typically triggered by

  • Drugs (eg, β-lactam antibiotics, insulin, streptokinase, allergen extracts)

  • Foods (eg, nuts, eggs, seafood)

  • Proteins (eg, tetanus antitoxin, blood transfusions)

  • Animal venoms

  • Latex

Peanut and latex allergens may be airborne. Occasionally, exercise or cold exposure (eg, in patients with cryoglobulinemia) can trigger or contribute to an anaphylactic reaction. History of atopy does not increase risk of anaphylaxis but increases risk of death when anaphylaxis occurs.


Interaction of antigen with IgE on basophils and mast cells triggers release of histamine, leukotrienes, and other mediators that cause diffuse smooth muscle contraction (eg, resulting in bronchoconstriction, vomiting, or diarrhea) and vasodilation with plasma leakage (eg, resulting in urticaria or angioedema).

Anaphylactoid reactions

These reactions are clinically indistinguishable from anaphylaxis but do not involve IgE and do not require prior sensitization. They occur via direct stimulation of mast cells or via immune complexes that activate complement. The most common triggers are iodinated radiopaque dye, aspirin, other NSAIDs, opioids, blood transfusions, Ig, and exercise.

Symptoms and Signs

Symptoms typically begin within 15 min of exposure and involve the skin, upper or lower airways, cardiovascular system, or GI tract. One or more areas may be affected, and symptoms do not necessarily progress from mild (eg, urticaria) to severe (eg, airway obstruction, refractory shock), although each patient typically manifests the same reaction to subsequent exposure.

Symptoms range from mild to severe and include flushing, pruritus, urticaria, sneezing, rhinorrhea, nausea, abdominal cramps, diarrhea, a sense of choking or dyspnea, palpitations, and dizziness.

Signs include hypotension, tachycardia, urticaria, angioedema, wheezing, stridor, cyanosis, and syncope. Shock can develop within minutes, and patients may have seizures, become unresponsive, and die. Cardiovascular collapse can occur without respiratory or other symptoms.

Late-phase reactions may occur 4 to 8 h after the exposure or later. Symptoms and signs are usually less severe than they were initially and may be limited to urticaria; however, they may be more severe or fatal.


Diagnosis is clinical. Anaphylaxis should be suspected if any of the following suddenly occur without explanation:

  • Shock

  • Respiratory symptoms (eg, dyspnea, stridor, wheezing)

  • Two or more other manifestations of possible anaphylaxis (eg, angioedema, rhinorrhea, GI symptoms)

Risk of rapid progression to shock leaves no time for testing, although mild equivocal cases can be confirmed by measuring 24-h urinary levels of N -methylhistamine or serum levels of tryptase. The cause is usually easily recognized based on history. If health care workers have unexplained anaphylactic symptoms, latex allergy should be considered (see Latex Sensitivity).

Pearls & Pitfalls

  • Consider latex allergy in health care workers with unexplained anaphylactic symptoms.


  • Epinephrine given immediately

  • Sometimes intubation

  • IV fluids and sometimes vasopressors for persistent hypotension

  • Antihistamines

  • Inhaled β-agonists for bronchoconstriction

Epinephrine is the cornerstone of treatment; it may help relieve all symptoms and signs and should be given immediately. It can be given sc or IM (usual dose is 0.3 to 0.5 mL of a 1:1000 [0.1%] solution in adults or 0.01 mL/kg in children, repeated every 10 to 30 min). Maximal absorption occurs when the drug is given IM in the lateral thigh. Patients with cardiovascular collapse or severe airway obstruction may be given epinephrine IV in a single dose (3 to 5 mL of a 1:10,000 [0.01%] solution over 5 min) or by continuous drip (1 mg in 250 mL 5% D/W for a concentration of 4 mcg/mL, starting at 1 mcg/min and titrated up to 4 mcg/min [15 to 60 mL/h]). Epinephrine may also be given by sublingual injection (0.5 mL of 1:1000 solution) or through an endotracheal tube (3 to 5 mL of a 1:10,000 solution diluted to 10 mL with saline). A second injection of epinephrine sc may be needed. Glucagon 1-mg bolus (20 to 30 mcg/kg in children) followed by 1-mg/h infusion should be used in patients taking oral β-blockers, which attenuate the effect of epinephrine.

Patients who have stridor and wheezing unresponsive to epinephrine should be given O2 and be intubated see Airway Establishment and Control : Tracheal Intubation. Early intubation is recommended because waiting for a response to epinephrine may allow upper airway edema to progress sufficiently to prevent endotracheal intubation and require cricothyrotomy.

Hypotension often resolves after epinephrine is given. Persistent hypotension can usually be treated with 1 to 2 L (20 to 40 mL/kg in children) of isotonic IV fluids (eg, 0.9% saline). Hypotension refractory to fluids and IV epinephrine may require vasopressors (eg, dopamine 5 mcg/kg/min).

Antihistamines—both H1 blockers (eg, diphenhydramine 50 to 100 mg IV) and H2 blockers (eg, cimetidine 300 mg IV)—should be given q 6 h until symptoms resolve. Inhaled β-agonists are useful for managing bronchoconstriction that persists after treatment with epinephrine; albuterol 5 to 10 mg by continuous nebulization can be given.

Corticosteroids have no proven role but may help prevent a late-phase reaction; methylprednisolone 125 mg IV initially is adequate.


Primary prevention is avoidance of known triggers. Desensitization is used for allergen triggers that cannot reliably be avoided (eg, insect stings). Patients with past reactions to radiopaque dye should not be reexposed. When exposure is absolutely necessary, patients are given 3 doses of prednisone 50 mg po q 6 h, starting 18 h before the procedure, and diphenhydramine 50 mg po 1 h before the procedure; however, evidence to support the efficacy of this approach is limited (see also Allergic-type contrast reactions).

Patients with an anaphylactic reaction to insect stings, foods, or other known substances should wear an alert bracelet and carry a prefilled epinephrine syringe (containing 0.3 mg for adults and 0.15 mg for children) for prompt self-treatment after exposure.

Key Points

  • Common triggers of anaphylaxis include drugs (eg, β-lactam antibiotics, allergen extracts), foods (eg, nuts, seafood), proteins (eg, tetanus antitoxin, blood transfusions), animal venoms, and latex.

  • Non–IgE-mediated reactions that have anaphylactic-like manifestations (anaphylactoid reactions) can be caused by iodinated radiopaque dye, aspirin, other NSAIDs, opioids, blood transfusions, Ig, and exercise.

  • Consider anaphylaxis if patients have unexplained hypotension, respiratory symptoms, or ≥ 2 anaphylactic manifestations (eg, angioedema, rhinorrhea, GI symptoms).

  • Give epinephrine immediately because anaphylactic symptoms may rapidly progress to airway occlusion or shock; epinephrine can help relieve all symptoms.

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* This is the Professional Version. *