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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.
Etiology
Anaphylaxis is typically triggered by
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.
Pathophysiology
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.
Diagnosis
Diagnosis is clinical. Anaphylaxis should be suspected if any of the following suddenly occur without explanation:
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 Sidebar 1: Allergic, Autoimmune, and Other Hypersensitivity Disorders: Latex Sensitivity ).
Treatment
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 μg/mL, starting at 1 μg/min and titrated up to 4 μg/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 μg/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. 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 μg/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 in 4 to 8 h; methylprednisolone 125 mg IV initially is adequate.
Prevention
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 Principles of Radiologic Imaging: 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
Last full review/revision July 2012 by Peter J. Delves, PhD
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