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 beta-agonists and sometimes endotracheal intubation. Persistent hypotension requires IV fluids and sometimes vasopressors.
(See also Overview of Allergic and Atopic Disorders.)
Anaphylaxis is a serious, systemic hypersensitivity reaction that is usually rapid in onset and is characterized by potentially life-threatening respiration and/or circulatory compromise (1).
The lifetime prevalence of anaphylaxis is estimated at 1.6 to 5.1% (1). Fatal anaphylaxis is rare.
Довідковий матеріал загального характеру
1. Golden DBK, Wang J, Waserman S, et al. Anaphylaxis: A 2023 practice parameter update. Ann Allergy Asthma Immunol 2024;132(2):124-176. doi: 10.1016/j.anai.2023.09.015
Etiology of Anaphylaxis
Anaphylaxis is typically triggered by
Medications (eg, beta-lactam antibiotics, insulin, streptokinase, allergen extracts)
Foods (eg, nuts, eggs, seafood)
Proteins (eg, tetanus antitoxin, blood transfusions)
Animal venoms
Latex
Peanut, latex, shellfish, and other 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 or angioedema).
Анафілактичні реакції
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)
Opioids
Monoclonal antibodies
Exercise
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, and/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. Therefore, patients who have an anaphylactic reaction should be observed in an acute care setting for several hours after the initial reaction.
Diagnosis of Anaphylaxis
History and physical examination
Sometimes measurement of serum levels of tryptase
Diagnosis of anaphylaxis 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 serum levels of tryptase (preferably within 2 hours of the reaction). 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 medications).
The cause is usually easily recognized based on history. If health care workers have unexplained anaphylactic symptoms, latex allergy should be considered.
Цінні поради та підводні камені
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Treatment of Anaphylaxis
Epinephrine given immediately
Sometimes intubation
IV fluids and sometimes vasopressors for persistent hypotension
Antihistamines
Inhaled beta-agonists for bronchoconstriction
Anaphylactoid reactions are treated similarly to anaphylactic reactions.
Епінефрин
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 epinephrine is given IM in the anterolateral (mid-outer) aspect of the thigh.
Management of cardiac arrest is per standard protocols. Patients with hypotension or severe airway obstruction may be given epinephrine IV or intraosseously (IO). A continuous drip using an infusion pump is preferred, but if the delay to prepare the drip and pump is unacceptable, epinephrine can be given as a single slow IV bolus dose of 0.05 to 0.1 mg (0.5 to 1 mL of a 0.1 mg/mL[1:10,000] solution over 1 to 2 minutes). For a continuous drip, 1 mg epinephrine is mixed in 250 mL 5% dextrose in water or 0.9% normal saline for a concentration of 4 mcg/mL and is started at 0.1 mcg/kg/minute and titrated up by 0.05 mcg/kg/minute every 2 to 3 minutes as needed based on blood pressure, heart rate, and oxygenation. If the patient's weight cannot be estimated accurately, the recommended starting dose for adults is 1 to 2 mcg/minute, titrated upward by 2 to 4 mcg/minute every 2 to 3 minutes. If an initial bolus is desired but IV access is delayed, 0.2 to 0.25 mg epinephrine may instead be given through an endotracheal tube (2 to 2.5 mL of a 0.1 mg/mL solution diluted to 5 to 10 mL with sterile water or saline); alternatively, a second IM dose of epinephrine may be given.
Beta-blocker therapy has been shown to be a risk factor for anaphylaxis. Based on epinephrine's mechanism of action, its efficacy may be decreased when used for the treatment of anaphylaxis if a patient is taking a beta-blocker. Despite this, because epinephrine is the most effective therapy for anaphylaxis, it should be used regardless of beta-blocker therapy. Although some studies do not support the decreased efficacy of epinephrine, it is still highly advised to avoid beta-blockers in situations that are at high risk of causing anaphylaxis, such as allergy immunotherapy or omalizumab administration (1, 2, 3). For patients taking oral beta-blockers, glucagon 1 to 5 mg IV over 5 minutes (20 to 30 mcg/kg in children) followed by a 5 to 15 mcg/minute infusion has been recommended. Rapid administration of glucagon can cause vomiting.
Інші методи лікування
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 isotonic IV fluids (eg, 0.9% saline). Hypotension that is refractory to fluids and IV epinephrine may require vasopressors (eg, dopamine).
Antihistamines—both H1 blockers (eg, diphenhydramine) and H2 blockers (eg, cimetidine)—should be given every 6 hours until symptoms resolve.
Inhaled beta-agonists (eg, albuterol) are useful for managing bronchoconstriction that persists after treatment with epinephrine.
Corticosteroids have no proven role but may help prevent a late-phase reaction.
Довідкові матеріали щодо лікування
1. White JL, Greger KC, Lee S, et al: Patients taking β-Blockers do not require increased doses of epinephrine for anaphylaxis. J Allergy Clin Immunol Pract 6 (5):1553–1558.e1, 2018. doi: 10.1016/j.jaip.2017.12.020
2. Sturm GJ, Herzog SA, Aberer W, et al: β-blockers and ACE inhibitors are not a risk factor for severe systemic sting reactions and adverse events during venom immunotherapy. Allergy 76 (7):2166–2176, 2021. doi: 10.1111/all.14785
3. Tejedor-Alonso MA, Farias-Aquino E, Elia Pérez-Fernández E, et al: Relationship between anaphylaxis and use of beta-blockers and angiotensin-converting enzyme inhibitors: A systematic review and meta-analysis of observational studies. J Allergy Clin Immunol Pract 7 (3):879–897.e5, 2019. doi: 10.1016/j.jaip.2018.10.042
Prevention of Anaphylaxis
Primary prevention of anaphylaxis is avoidance of known triggers. Desensitization is used for allergen triggers that cannot reliably be avoided (eg, insect stings).
Patients with past anaphylactoid reactions to a radiopaque contrast agent 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.
Omalizumab can be used for prevention of type 1 allergic reactions (including anaphylaxis) that may occur with accidental exposure to 1 or more foods in patients ≥ 1 year old with IgE-mediated food allergy .
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.
Ключові моменти
Common triggers of anaphylaxis include medications (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.
