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Signs and symptoms

Involvement of body organ systems in anaphylaxis varies among patients, and even in the same patient from one allergic reaction to another. However, there are general patterns regarding organ system involvement and signs and symptoms associated with anaphylaxis.1-3

Most often, allergic reactions involve the skin (80%-90%) and the respiratory tract (70%).3,4 Less often, allergic reactions involve the GI tract (30%-45%), the cardiovascular system (10%-45%) and the central nervous system (10%-15%).3,4 See Table 1. Symptoms involving the throat, lungs or heart can potentially be life-threatening and should not be ignored. See Table 2.3,5

Table 1. Common Signs and Symptoms of Anaphylaxis3,5,6

Skin Airway* Central Nervous System Cardiovascular System* GI Tract
80-90% of reactions 70% of reactions 10-15% of reactions 10-45% of reactions 30-45% of reactions
Hives (urticarial), itching (pruritus), flushing Larynx: pruritus and tightness in throat; dysphonia and hoarseness Uneasiness, throbbing headache, dizziness, confusion, tunnel vision Chest pain, hypotension, tachycardia, weak pulse, dizziness, fainting Nausea, cramping, abdominal pain, vomiting, diarrhea
Mucosal tissue: pruritus and swelling of lips, tongue, uvula/palate Lung: dyspnea, chest tightness, wheezing/bronchospasm

*Potentially life-threatening symptoms.

Table 2. Major organs and symptoms implicated in anaphylaxis1,3

Throat Lung Heart
Pruritus and tightness in the throat Dyspnea Chest pain
Dysphonia Chest tightness Hypotension
Hoarseness Wheezing/
bronchospasm 		Tachycardia


Weak pulse


Dizziness


Fainting

Confirmation of anaphylaxis triggers

In patients who have experienced anaphylaxis, it is important to confirm the allergic trigger or triggers.3,6 A detailed history of prior exposures and resulting allergic reactions can identify specific allergic triggers that should be avoided in order to prevent recurrences of anaphylaxis.2,3,6

Determining the nature of the symptoms during previous anaphylactic reactions is also important. It is critical to ask the patient if there was2:

  • Evidence of skin manifestations, particularly angioedema, flushing, pruritus or urticaria
  • Upper or lower airway obstruction
  • Nausea, vomiting, diarrhea or other GI symptoms
  • Syncope/presyncopal symptoms

In addition to the patient’s history, several tests are available to help identify allergic triggers of anaphylaxis, including skin tests, in vitro tests and challenge tests.3 These tests are described in Table 3.

Table 3. Tests that confirm anaphylactic triggers

Skin tests
  • Determine the presence of IgE antibodies and identify anaphylactic reactions triggered by food, medications and stinging or biting insects3
  • Skin tests are performed at least 3 to 4 weeks after an anaphylactic reaction3
  • In the case of a skin prick/puncture test, a positive result is indicated by a mean wheal diameter of 3 mm or greater7
In vitro tests
  • Determine the presence of allergen-specific IgE levels in the serum and identify anaphylactic reactions triggered by food, biting or stinging insects, medications and latex3
  • In vitro tests are considered less sensitive than skin tests2,5
  • ImmunoCAP is an example of a quantitative in vitro test that correlates IgE levels with clinical reactivity and has predictive values for positive or negative results8
Challenge tests
  • Physician-monitored challenge tests may be used if skin or in vitro test results are inconclusive2
  • Challenge tests help predict the clinical reactivity to anaphylaxis triggered by food and medication3
  • Challenge tests are time-consuming, costly and risky, and should be conducted only in well-equipped healthcare facilities staffed by healthcare professionals who are trained and experienced in selecting appropriate patients for these tests, performing challenges and diagnosing and treating anaphylaxis2,3
  • Challenge tests should not be performed in patients with a documented history of food-related anaphylaxis due to an increased risk of triggering an attack3

Anaphylaxis diagnosis criteria

The following diagnostic criteria (see Table 4) are likely to capture more than 95% of cases of anaphylaxis.9

Table 4. Clinical criteria for diagnosing anaphylaxis9

Anaphylaxis is highly likely when any one of the following 3 criteria is fulfilled:

Because the majority of anaphylactic reactions (>80%) include skin symptoms, it was judged that at least 80% of anaphylactic reactions should be identified by criterion 1—even when the allergic status of the patient and potential cause of the reaction are unknown. However, cutaneous symptoms might be absent in up to 20% of anaphylactic reactions in children with food or insect sting or bite allergy.

Criterion 1. Acute onset of an illness (minutes to several hours) with involvement of the skin, mucosal tissue or both (e.g., generalized hives, pruritus or flushing, swollen lips/tongue/uvula)

AND AT LEAST ONE OF THE FOLLOWING:

  1. Respiratory compromise (e.g., dyspnea, wheeze-bronchospasm, stridor, reduced peak expiratory function [PEF], hypoxemia)
  2. Reduced blood pressure (BP) or associated symptoms of end-organ dysfunction (e.g., hypotonia [collapse], syncope, incontinence)
In patients with a known allergic history and possible exposure, criterion 2 should provide ample evidence that an anaphylactic reaction is occurring.

Criterion 2. Two or more of the following that occur rapidly after exposure to a likely allergen for that patient (minutes to several hours):

  1. Involvement of the skin-mucosal tissue (e.g., generalized hives, itch-flush, swollen lips/tongue/uvula)
  2. Respiratory compromise (e.g., dyspnea, wheeze-bronchospasm, stridor, reduced PEF, hypoxemia)
  3. Reduced BP or associated symptoms (e.g., hypotonia [collapse], syncope, incontinence)
  4. Persistent GI symptoms (e.g., cramping abdominal pain, vomiting)
Criterion 3 should identify the rare patients who experience an acute hypotensive episode after exposure to a known allergen.

Criterion 3. Reduced BP after exposure to known allergen for that patient (minutes to several hours):

  1. Children: low systolic BP* (age-specific) or greater than 30% decrease in systolic BP
  2. Adults: systolic BP of less than 90 mm Hg or greater than 30% decrease from that person’s baseline

*Low systolic BP for children is defined as <70 mm Hg from 1 month to 1 year; < (70 mm Hg + [2 X age]) from 1 year to 10 years; and <90 mm Hg from 11 to 17 years. Adapted from Sampson et al, J Allergy Clin Immunol, 2006.

Identifying patients at risk for an anaphylactic reaction

Major risk factors for a recurrent anaphylactic reaction include a history of previous anaphylaxis, exposure to allergic triggers and atopy.2 However, the severity of previous allergic reactions is not always indicative of the severity of future reactions.2,6,10

There are factors that increase the risk of anaphylaxis, such as exposure to known allergens, as well as factors that may increase the risk of a severe anaphylactic reaction, such as concomitant diseases and medications that hinder a patient from recognizing the signs and symptoms of anaphylaxis.3 A complete description of these risk factors can be found in Tables 5 and 6.

Table 5. Factors that increase the risk of experiencing anaphylaxis3

Allergens

Exposure to certain allergens increases the risk of triggering an anaphylactic reaction for those who are allergic, including:

  • Foods such as peanuts, tree nuts, fish, shellfish, eggs and milk
  • Biting or stinging insects such as bees, ants and ticks
  • Latex
  • Medications such as β-lactam antibiotics (e.g., penicillin)
Other factors
  • Exercise
  • Exposure to temperature extremes or UV radiation

Table 6. Factors that may increase anaphylaxis severity3

Age
  • Adolescents and young adults may be at increased risk for more severe anaphylaxis because of inconsistent behaviors in avoiding their confirmed allergic triggers
  • The elderly may be at increased risk of life-threatening anaphylactic reactions because of concomitant diseases, including chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD), and medications used to treat them. In addition, the elderly may be at an increased risk of having a more severe anaphylactic reaction if they are exposed to biting or stinging insects
Comorbidities

The following concomitant diseases are associated with an increased risk of a severe anaphylactic reaction:

  • Respiratory diseases such as asthma, especially if severe or uncontrolled
  • Chronic respiratory diseases such as COPD, especially if severe or uncontrolled
  • CVDs such as coronary heart disease and hypertension
  • Mastocytosis or clonal mast cell disorders
  • Atopic diseases (e.g., allergic rhinitis, eczema)

In patients of any age, concomitant diseases hampering recognition of signs and symptoms of anaphylaxis may place patients at an increased risk of a more severe anaphylactic reaction. Such diseases include:

  • Impaired vision or hearing
  • Neurologic disorders such as seizures
  • Psychiatric disorders such as depression
  • Autism spectrum disorder
Concurrent medication or chemical use

In patients of any age, concurrent medications and chemicals hampering recognition of signs and symptoms of anaphylaxis may place patients at an increased risk of anaphylaxis. Such medications and/or chemicals include:

  • First-generation H1-antihistamines such as diphenhydramine and chlorpheniramine
  • Antidepressants
  • Sedatives
  • Hypnotics
  • CNS-active chemicals such as ethanol
  • Recreational drugs

Medications that may increase the severity of anaphylactic reactions and make them more difficult to treat include:

  • β-blockers, which potentially decrease epinephrine efficacy by blocking effects at adrenergic receptors
  • Angiotensin-converting enzyme (ACE) inhibitors, which potentially interfere with endogenous compensatory responses

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Important Safety Information (the following information applies to both EPIPEN and its Authorized Generic)

EPIPEN (epinephrine injection, USP) 0.3 mg and EPIPEN JR (epinephrine injection, USP) 0.15 mg Auto-Injectors are intended for immediate administration as emergency supportive therapy only and are not intended as a substitute for immediate medical or hospital care. In conjunction with the administration of epinephrine, the patient should seek immediate medical or hospital care. More than two sequential doses of epinephrine should only be administered under direct medical supervision.

EPIPEN and EPIPEN JR should only be injected into the anterolateral aspect of the thigh. Do not inject intravenously, into buttock, or into digits, hands, or feet. Instruct caregivers to hold the leg of young children firmly in place and limit movement prior to and during injection to minimize risk of injection-related injury.

Rare cases of serious skin and soft tissue infections have been reported following epinephrine injection. Advise patients to seek medical care if they develop symptoms of infection such as persistent redness, warmth, swelling, or tenderness at the injection site.

Epinephrine should be used with caution in patients with heart disease, and in patients who are on drugs that may sensitize the heart to arrhythmias, because it may precipitate or aggravate angina pectoris and produce ventricular arrhythmias. Arrhythmias, including fatal ventricular fibrillation, have been reported, particularly in patients with underlying cardiac disease or taking cardiac glycosides, diuretics, or anti-arrhythmics.

Patients with certain medical conditions or who take certain medications for allergies, depression, thyroid disorders, diabetes, and hypertension, may be at greater risk for adverse reactions. Common adverse reactions to epinephrine include anxiety, apprehensiveness, restlessness, tremor, weakness, dizziness, sweating, palpitations, pallor, nausea and vomiting, headache, and/or respiratory difficulties.

Indications (the following information applies to both EPIPEN and its Authorized Generic)

EPIPEN and EPIPEN JR Auto-Injectors are indicated in the emergency treatment of allergic reactions (Type I) including anaphylaxis to stinging insects (e.g., order Hymenoptera, which include bees, wasps, hornets, yellow jackets and fire ants) and biting insects (e.g., triatoma, mosquitoes), allergen immunotherapy, foods, drugs, diagnostic testing substances (e.g., radiocontrast media) and other allergens, as well as idiopathic anaphylaxis or exercise-induced anaphylaxis. EPIPEN and EPIPEN JR Auto-Injectors are intended for immediate administration in patients who are determined to be at increased risk for anaphylaxis, including individuals with a history of anaphylactic reactions.

Click here for Full Prescribing Information for EPIPEN.
Click here for Full Prescribing Information for the Authorized Generic for EPIPEN.

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Important Safety Information (the following information applies to both EPIPEN and its Authorized Generic)

EPIPEN (epinephrine injection, USP) 0.3 mg and EPIPEN JR (epinephrine injection, USP) 0.15 mg Auto-Injectors are intended for immediate administration as emergency supportive therapy only and are not intended as a substitute for immediate medical or hospital care. In conjunction with the administration of epinephrine, the patient should seek immediate medical or hospital care. More than two sequential doses of epinephrine should only be administered under direct medical supervision.

Rare cases of serious skin and soft tissue infections have been reported following epinephrine injection.

Important Safety Information (the following information applies to both Epipen and its Authorized Generic)

EPIPEN (epinephrine injection, USP) 0.3 mg and EPIPEN JR (epinephrine injection, USP) 0.15 mg Auto-Injectors are intended for immediate administration as emergency supportive therapy only and are not intended as a substitute for immediate medical or hospital care. In conjunction with the administration of epinephrine, the patient should seek immediate medical or hospital care. More than two sequential doses of epinephrine should only be administered under direct medical supervision.

EPIPEN and EPIPEN JR should only be injected into the anterolateral aspect of the thigh. Do not inject intravenously, into buttock, or into digits, hands, or feet. Instruct caregivers to hold the leg of young children firmly in place and limit movement prior to and during injection to minimize risk of injection-related injury.

Rare cases of serious skin and soft tissue infections have been reported following epinephrine injection. Advise patients to seek medical care if they develop symptoms of infection such as persistent redness, warmth, swelling, or tenderness at the injection site.

Epinephrine should be used with caution in patients with heart disease, and in patients who are on drugs that may sensitize the heart to arrhythmias, because it may precipitate or aggravate angina pectoris and produce ventricular arrhythmias. Arrhythmias, including fatal ventricular fibrillation, have been reported, particularly in patients with underlying cardiac disease or taking cardiac glycosides, diuretics, or anti-arrhythmics.

Patients with certain medical conditions or who take certain medications for allergies, depression, thyroid disorders, diabetes, and hypertension, may be at greater risk for adverse reactions. Common adverse reactions to epinephrine include anxiety, apprehensiveness, restlessness, tremor, weakness, dizziness, sweating, palpitations, pallor, nausea and vomiting, headache, and/or respiratory difficulties.

Indications (the following information applies to both EPIPEN and its Authorized Generic)

EPIPEN and EPIPEN JR Auto-Injectors are indicated in the emergency treatment of allergic reactions (Type I) including anaphylaxis to stinging insects (e.g., order Hymenoptera, which include bees, wasps, hornets, yellow jackets and fire ants) and biting insects (e.g., triatoma, mosquitoes), allergen immunotherapy, foods, drugs, diagnostic testing substances (e.g., radiocontrast media) and other allergens, as well as idiopathic anaphylaxis or exercise-induced anaphylaxis. EPIPEN and EPIPEN JR Auto-Injectors are intended for immediate administration in patients who are determined to be at increased risk for anaphylaxis, including individuals with a history of anaphylactic reactions.

Click here for Full Prescribing Information for EPIPEN.
Click here for Full Prescribing Information for the Authorized Generic for EPIPEN.

  • About Anaphylaxis
  • About EPIPEN  and Its Authorized Generic
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    • References

    1. Dinakar C. Anaphylaxis in children: current understanding and key issues in diagnosis and treatment. Curr Allergy Asthma Rep. 2012;12(6):641-649.
    2. Lieberman P, Nicklas RA, Randolph C,et al. Anaphylaxis—a practice parameter update 2015. Ann Allergy Asthma Immunol. 2015;115(5):341-384.
    3. Simons FE. Anaphylaxis. J Allergy Clin Immunol. 2010;125(2)(suppl 2):S161-S181.
    4. Simons FE. Anaphylaxis: recent advances in assessment and treatment. J Allergy Clin Immunol. 2009;124(4):625-636.
    5. Volcheck GW. Clinical Allergy: Diagnosis and Management. Rochester, MN: Mayo Foundation for Medical Education and Research; 2009.
    6. Simons FE, Ardusso LR, Bilὸ MB, et al; World Allergy Organization. World Allergy Organization guidelines for the assessment and management of anaphylaxis. World Allergy Organ J. 2011;4(2):13-37.
    7. Bousquet J, Heinzerling L, Bachert C,et al. Practical guide to skin prick tests in allergy to aeroallergens. Allergy. 2012;67(1):18-24.
    8. Johansson SG. ImmunoCAP specific IgE test: an objective tool for research and routine allergy diagnosis. Expert Rev Mol Diagn. 2004;4(3):273-289.
    9. Sampson HA, Muñoz-Furlong A, Campbell RL, et al. Second symposium on the definition and management of anaphylaxis: summary report—Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium. J Allergy Clin Immunol. 2006;117(2):391-397.
    10. Boyce JA, Assa’ad A, Burks AW, et al. Guidelines for the diagnosis and management of food allergy in the United States: report of the NIAID-sponsored expert panel. J Allergy Clin Immunol. 2010;126(6):S1-S58.
  • About Anaphylaxis
  • About EPIPEN  and Its Authorized Generic
  • For Healthcare Partners
  • Access to EPIPEN  and Its Authorized Generic
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