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Am Fam Physician. 2020;102(6):355-362

Patient information: A handout on this topic is available at https://familydoctor.org/condition/anaphylaxis/.

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Anaphylaxis is a life-threatening systemic reaction, normally occurring within one to two hours of exposure to an allergen. The incidence of anaphylaxis in the United States is 2.1 per 1,000 person-years. Most anaphylactic reactions occur outside the hospital setting. Urticaria, difficulty breathing, and mucosal swelling are the most common symptoms of anaphylaxis. The most common triggers are medications, stinging insect venoms, and foods; however, unidentified triggers occur in up to one-fifth of cases. Coexisting asthma, mast cell disorders, older age, underlying cardiovascular disease, peanut and tree nut allergy, and drug-induced reactions are associated with severe or fatal anaphylactic reactions. Clinicians can obtain serum tryptase levels, reflecting mast cell degranulation, when the clinical diagnosis of anaphylaxis is not clear. Acute management of anaphylaxis involves removal of the trigger; early administration of intramuscular epinephrine; supportive care for the patient's airway, breathing, and circulation; and a period of observation for potential biphasic reactions. Only after epinephrine administration should adjunct medications be considered; these include histamine H1 and H2 antagonists, corticosteroids, beta2 agonists, and glucagon. Patients should be monitored for a biphasic reaction (i.e., recurrence of anaphylaxis without reexposure to the allergen) for four to 12 hours, depending on risk factors for severe anaphylaxis. Following an anaphylactic reaction, management should focus on developing an emergency action plan, referral to an allergist, and patient education on avoidance of triggers and appropriate use of an epinephrine auto-injector.

Anaphylaxis is a severe allergic reaction that occurs quickly and can be fatal. The incidence of anaphylaxis in the United States between 2004 and 2016 was 2.1 per 1,000 person-years, with one-fourth of anaphylactic reactions affecting children younger than 17 years.1 Most anaphylactic reactions occur outside the hospital setting (Table 1),2,3 and most individuals go to the hospital or emergency department for treatment.2,4 In the United States, the incidence of anaphylaxis peaks in children two to 12 years of age and in adults between 50 and 69 years of age.1 One out of 20 of all anaphylaxis cases may require hospitalization1,2; in the United States, hospitalizations for anaphylaxis have steadily increased over the past 10 years.5 The annual number of confirmed anaphylaxis-related deaths in the United States ranges from 186 to 225.5 The average fatality rate is 0.3% for most hospitalizations or emergency department presentations for anaphylaxis.5 Risk factors for severe or fatal anaphylaxis include coexisting asthma, mast cell disorders, age older than 50 years, underlying cardiovascular disease, peanut and tree nut allergy, and drug-induced reactions.610

WHAT'S NEW ON THIS TOPIC

One out of 20 of all anaphylaxis cases requires hospitalization; in the United States, hospitalizations for anaphylaxis have steadily increased over the past 10 years.

Gastrointestinal and respiratory symptoms of anaphylaxis are more likely to be overlooked in children. Only 55% of health care professionals recognize anaphylaxis without cutaneous involvement.

One-half of patients presenting to the emergency department who meet the National Institute of Allergy and Infectious Diseases/Food Allergy and Anaphylaxis Network diagnostic criteria for anaphylaxis receive treatment with epinephrine.

Clinical recommendationEvidence ratingComments
Administer intramuscular epinephrine into the anterolateral thigh as the first-line treatment of anaphylaxis.8,10,25,26,33,34 BConsistent cohort studies showing decreased mortality and hospitalization from early epinephrine administration
Use histamine H1 and H2 antagonists and corticosteroids only as adjunct therapies after the administration of epinephrine.8,11,25 CExpert opinion and consensus guideline in the absence of clinical trials
Use fluid resuscitation (1 to 2 L of 0.9% isotonic saline at a rate of 5 to 10 mL per kg for adults in the first five to 10 minutes; 10 mL per kg for children) in anaphylactic patients with hypotension that does not respond to epinephrine.8,11,35 CExpert opinion and consensus guideline in the absence of clinical trials
Individualize observation for a biphasic reaction; strongly consider observation for a minimum of four hours following an episode of anaphylaxis and six to 12 hours for patients who have risk factors for severe anaphylaxis, a previous biphasic reaction, a previous protracted anaphylactic event, unknown inciting trigger, severe initial presentation, or who required more than one dose of epinephrine treatment.8,11,25,4446 CExpert opinion and consensus guideline in the absence of clinical trials
Prescribe auto-injectable epinephrine to all patients at risk for an anaphylactic reaction, and provide an action plan instructing them on how and when to administer the medication.8,11,25,47 CExpert opinion and consensus guideline in the absence of clinical trials
RecommendationSponsoring organization
Do not rely on antihistamines as first-line treatment in severe allergic reactions.American Academy of Allergy, Asthma, and Immunology
Home41% to 51%
Hospital or medical clinic14%
Family member's or friend's home7%
Workplace6%
Restaurant5% to 6%
School3% to 6%
During travel5%
Outdoors3%

Pathophysiology

There are two types of anaphylactic reactions: immunoglobulin E (IgE) mediated and nonimmune (i.e., direct activation).11 Most cases of anaphylaxis are IgE mediated in which antibodies to a particular allergen activate mast cells and basophils, resulting in degranulation and release of a wide variety of chemical mediators. Nonimmune anaphylaxis occurs by direct activation of mast cell and basophil receptors or complement-mediated activation. Distinction between the two types is not clinically possible, and treatment is the same for both.11

Diagnosis

Clinicians should be familiar with the differential diagnosis of anaphylaxis because many other conditions can present with signs or symptoms of anaphylaxis (Table 211,12 ). Signs and symptoms of an allergic reaction typically occur within one to two hours of exposure to an allergen, usually within 30 minutes for a food allergy and faster for parenteral medication or insect stings. Most acute allergic reactions are mild and self-limited, involving a single organ system, often the skin, with symptoms such as swelling of the lips or face, hives or welts, or tingling of the mouth. Anaphylaxis is distinguished from a mild or moderate allergic reaction by the sudden involvement of two or more organ systems manifesting with a variety of symptoms such as difficulty breathing, swelling of the tongue, swelling or tightness in the throat, wheezing, sudden persistent cough, abdominal pain, vomiting, and hypotension13 (Table 314 ). Anaphylaxis can also be diagnosed by the isolated involvement of the cardiovascular system in the setting of hypotension or cardiovascular collapse after exposure to a known allergen.14 Although isolated hypotension is a rare presentation of anaphylaxis, it often results in hospitalization and can be a marker of severity.15

PresentationDifferential diagnosis
Flush syndromeAutonomic epilepsy
Carcinoid
Medullary carcinoma of the thyroid
Perimenopausal hot flashes
Red man syndrome (i.e., adverse reaction to vancomycin)
HypotensionCardiogenic shock
Hypovolemic shock
Septic shock
Vasovagal reaction
MiscellaneousAnxiety, panic attacks
Hereditary angioedema
Leukemia with excess histamine production
Systemic mastocytosis
Postprandial collapseAirway foreign body
Monosodium glutamate ingestion
Scombroid fish poisoning
Sulfite ingestion
Respiratory distress with wheezing or stridorAspiration of a foreign body
Asthma and chronic obstructive pulmonary disease exacerbation
Vocal cord dysfunction syndrome
Anaphylaxis is highly likely when any one of the following three sets of criteria is met:
Acute onset of an illness (i.e., minutes to several hours) with involvement of the skin, mucosal tissue, or both (e.g., generalized hives; pruritus or flushing; swollen lips, tongue, or uvula; and at least one of the following:
 Respiratory compromise (e.g., dyspnea, wheezing, bronchospasm, stridor, reduced peak expiratory flow, hypoxemia)
 Reduced blood pressure or associated symptoms of end-organ dysfunction (e.g., hypotonia [collapse], syncope, incontinence)
Two or more of the following that occur rapidly (i.e., minutes to several hours) after exposure to a likely allergen for that patient:
 Involvement of the skin, mucosal tissue, or both (e.g., generalized hives; pruritus or flushing; swollen lips, tongue, or uvula)
 Respiratory compromise (e.g., dyspnea, wheezing, bronchospasm, stridor, reduced peak expiratory flow, hypoxemia)
 Reduced blood pressure or associated symptoms (e.g., hypotonia [collapse], syncope, incontinence)
 Persistent gastrointestinal symptoms (e.g., abdominal cramps, vomiting)
Reduced blood pressure that occurs rapidly (i.e., minutes to several hours) after exposure to a known allergen for that patient
 Infants and children: low systolic blood pressure (age-specific)* or a 30% or greater decrease in systolic blood pressure
 Adults: systolic blood pressure of less than 90 mm Hg or a 30% or greater decrease from baseline

Making an accurate diagnosis is important because epinephrine is administered more often to patients diagnosed with anaphylaxis.16,17 Clinicians must be familiar with and recognize the wide spectrum of presentations to avoid a missed diagnosis (Table 42,4,16,1822 ). For example, syncope and hypotension are more common presentations in drug-induced anaphylaxis,7 and in children, gastrointestinal and respiratory symptoms are more likely to be overlooked despite the more common occurrence of gastrointestinal symptoms.18,23 In one study, only 55% of health care professionals recognized anaphylaxis without cutaneous involvement.24

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