(See also Overview of Allergic and Atopic Disorders Overview of Allergic and Atopic Disorders Allergic (including atopic) and other hypersensitivity disorders are inappropriate or exaggerated immune reactions to foreign antigens. Inappropriate immune reactions include those that are... read more .)
Etiology of Anaphylaxis
Anaphylaxis is typically triggered by
Drugs (eg, beta-lactam antibiotics, insulin, streptokinase, allergen extracts)
Foods (eg, nuts, eggs, seafood)
Proteins (eg, tetanus antitoxin, blood transfusions)
Peanut and latex allergens may be airborne. Occasionally, exercise or cold exposure 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 of Anaphylaxis
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 Urticaria Urticaria consists of migratory, well-circumscribed, erythematous, pruritic plaques on the skin. Urticaria also may be accompanied by angioedema, which results from mast cell and basophil activation... read more or angioedema Angioedema Angioedema is edema of the deep dermis and subcutaneous tissues. It is usually an acute mast cell–mediated reaction caused by exposure to drug, venom, dietary, pollen, or animal dander allergens... read more ).
Anaphylactoid 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 of anaphylactoid reactions are
Iodinated radiopaque contrast agents
Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs)
Symptoms and Signs of Anaphylaxis
Symptoms of anaphylaxis typically begin within 15 minutes of exposure and involve the skin, upper or lower airways, cardiovascular system, or gastrointestinal (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 of anaphylaxis 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 hours 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 of Anaphylaxis
Sometimes measurement of 24-hour urinary levels of N-methylhistamine or serum levels of tryptase
Diagnosis of anaphylaxis is clinical. Anaphylaxis should be suspected if any of the following suddenly occur without explanation:
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-hour urinary levels of N-methylhistamine or serum levels of tryptase. During anaphylaxis, these levels are elevated, and measuring them can help confirm the diagnosis if it is unclear or if the symptoms recur (eg, after treatment with IV drugs).
Pearls & Pitfalls
Treatment of Anaphylaxis
Epinephrine given immediately
IV fluids and sometimes vasopressors for persistent hypotension
Inhaled beta-agonists for bronchoconstriction
Epinephrine is the cornerstone of treatment for anaphylaxis; it may help relieve all symptoms and signs and should be given immediately.
Epinephrine can be given subcutaneously 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 5 to 15 minutes). Maximal absorption occurs when the drug is given IM in the anterolateral aspect of the thigh.
Patients with cardiovascular collapse or severe airway obstruction may be given epinephrine IV or intraosseously (IO) in a single dose (0.5 to 1 mL of a 1:10,000 [0.01%] solution) or by continuous drip (1 mg in 250 mL 5% D/W for a concentration of 4 mcg/mL, starting at 1 mcg/minute and titrated up to 4 mcg/minutes [15 to 60 mL/hour]). Epinephrine may also be given through an endotracheal tube (2 to 2.5 mL of a 1:10,000 solution diluted to 5 to 10 mL with sterile water or saline). A second subcutaneous injection of epinephrine may be needed.
Glucagon 1-mg bolus (20 to 30 mcg/kg in children) followed by 1-mg/hour infusion should be used in patients taking oral beta-blockers, which attenuate the effect of epinephrine.
Patients who have stridor and wheezing unresponsive to epinephrine should be given oxygen 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 mcg/kg/minute).
Antihistamines—both H1 blockers (eg, diphenhydramine 50 to 100 mg IV) and H2 blockers (eg, cimetidine 300 mg IV)—should be given every 6 hours until symptoms resolve.
Inhaled beta-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.
Prevention of Anaphylaxis
Primary prevention of anaphylaxis is avoidance of known triggers. Desensitization Immunotherapy Allergic (including atopic) and other hypersensitivity disorders are inappropriate or exaggerated immune reactions to foreign antigens. Inappropriate immune reactions include those that are... read more is used for allergen triggers that cannot reliably be avoided (eg, insect stings).
Patients with past anaphylactoid reactions to a radiopaque contrast agent Allergic-type contrast reactions Radiopaque contrast agents are often used in radiography and fluoroscopy to help delineate borders between tissues with similar radiodensity. Most contrast agents are iodine based. Iodinated... read more should not be reexposed. When exposure is absolutely necessary, patients are given 3 doses of prednisone 50 mg orally every 6 hours, starting 18 hours before the procedure, and diphenhydramine 50 mg orally 1 hour before the procedure; however, evidence to support the efficacy of this approach is limited.
Patients with an anaphylactic reaction to insect stings, foods, or other known substances should wear an alert bracelet and carry a prefilled, self-injecting epinephrine syringe (containing 0.3 mg for adults and 0.15 mg for children) and oral antihistamines for prompt self-treatment after exposure. If a severe reaction occurs, patients should be advised to use these treatments as quickly as possible and then go to the emergency department. There, they can be closely monitored and treatment can be repeated or adjusted as needed.
Common triggers of anaphylaxis include drugs (eg, beta-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 an iodinated radiopaque contrast agent, aspirin, other nonsteroidal anti-inflammatory drugs, opioids, monoclonal antibodies, and exercise.
Consider anaphylaxis if patients have unexplained hypotension, respiratory symptoms, or ≥ 2 anaphylactic manifestations (eg, angioedema, rhinorrhea, gastrointestinal symptoms).
Give epinephrine immediately because anaphylactic symptoms may rapidly progress to airway occlusion or shock; epinephrine can help relieve all symptoms.
Instruct patients to always wear an alert bracelet and carry a prefilled, self-injecting epinephrine syringe for prompt self-treatment after exposure.
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