(See also Overview of Allergic and Atopic Disorders.)
The prevalence of anaphylaxis is difficult to ascertain, but one study using 2 nationwide public surveys suggested that it was about 1.6% in the general adult population. Fatal anaphylaxis is far less common; it occurs in < 1 per million population (1).
General reference
1. Ma L, Danoff TM, Borish L: Case fatality and population mortality associated with anaphylaxis in the United States. J Allergy Clin Immunol 133 (4):1075–1083, 2014. doi: 10.1016/j.jaci.2013.10.029
Etiology of Anaphylaxis
Anaphylaxis is typically triggered by
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 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).
Anaphylactoid reactions
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
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
Clinical evaluation
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 drugs).
The cause is usually easily recognized based on history. If health care workers have unexplained anaphylactic symptoms, latex allergy should be considered.
Pearls & Pitfalls
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Treatment of Anaphylaxis
Sometimes intubation
IV fluids and sometimes vasopressors for persistent hypotension
Antihistamines
Inhaled beta-agonists for bronchoconstriction
Anaphylactoid reactions are treated similarly to anaphylactic reactions.
Epinephrine
Other treatments
Treatment references
1. White JL, Greger KC, Lee S, et alJ 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
Key Points
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.
Consider anaphylaxis if patients have unexplained hypotension, respiratory symptoms, or ≥ 2 anaphylactic manifestations (eg, angioedema, rhinorrhea, gastrointestinal symptoms).
More Information
The following English-language resource may be helpful. Please note that THE MANUAL is not responsible for the content of this resource.
Anaphylaxis—a 2020 practice parameter update, systematic review, and grading of recommendations, assessment, development and evaluation (GRADE) analysis. This article discusses the epidemiology, risk factors, pathogenesis, diagnosis, and treatment of anaphylaxis. It evaluates the relative benefits and harms of supplemental glucocorticoids and/or antihistamine premedication to prevent anaphylaxis and the evidence for these treatments. The article also provides recommendations for treatment.
