Highlights & Basics
- Sudden onset of respiratory or cardiovascular compromise, usually with a history of allergen exposure in sensitized individuals.
- Skin rash, wheezing and inspiratory stridor, hypotension, anxiety, nausea, and vomiting are the cardinal signs and symptoms.
- The diagnosis is clinical. Allergy testing is helpful only for secondary prophylaxis.
- Securing the airway and initiating prompt treatment with epinephrine (adrenaline) may save lives.
- Comorbidities (e.g., coronary artery disease and COPD) may pose a treatment challenge and warrant expert consultation
Quick Reference
History & Exam
Key Factors
acute onset
urticaria
angioedema
flushing
dyspnea
wheezing
rhinitis
Other Factors
allergen ingestion
insect stings or bites
pruritus
inspiratory stridor and hoarse voice
bilateral conjunctivitis
nausea and vomiting
abdominal cramping or pain
agitation/anxiety
confusion/disorientation
tachycardia
dizziness
syncope
sense of impending doom (angor animi)
recent exercise
hot or cold exposure
hypotension
bradycardia
cardiac arrest
diarrhea
visual disturbances
tremor
seizures
Diagnostics Tests
1st Tests to Order
serum tryptase level
Other Tests to consider
in vitro IgE testing
skin test
challenge test
Emerging Tests
basophil activation test
Treatment Options
presumptive
all patients: acute onset
all patients: acute onset
cardiopulmonary arrest
severe hypotension
persistent respiratory symptoms
symptomatic hives and rhinorrhea
post-emergency stabilization
Definition
Classifications
Classification of anaphylaxis according to causative mechanism
- food
- airborne allergens
- latex
- venom
- medication
- alpha-gal
- food-dependent, exercise-induced anaphylaxis
- hormones
- seminal fluid
- radiocontrast media
- immune aggregate
- intravenous immunoglobulin
- medication
- radiocontrast media
- opiates
- physical factors (e.g., exercise, cold, heat)
- increased mast cell sensitivity/degranulation
- unrecognized allergens
- Munchausen stridor
- vocal cord dysfunction
Allergic Diseases Resource Center classification
- Anaphylaxis: immunologic, particularly IgE-mediated reactions
- Nonallergic anaphylaxis: clinically identical to anaphylaxis; however, not immunologically mediated.
Vignette
Common Vignette 1
Common Vignette 2
Other Presentations
Epidemiology
Etiology
Pathophysiology
Diagnostic Approach
History
Clinical presentation
Laboratory evaluation in acute setting
Laboratory testing to prevent recurrence
Risk Factors
History & Exam
Tests
Differential Diagnosis
Septic shock
Differentiating Signs/Symptoms
- Absence of previous allergic reactions, lack of allergen exposure, slower onset, fever, and other signs of localized infection often differentiate septic shock from anaphylaxis.
Differentiating Tests
- Increased WBC count and increased temperature.
- Chest x-ray with a pulmonary infiltrate is suggestive of underlying pneumonia as source of infection.
Cardiogenic shock
Differentiating Signs/Symptoms
- Age, risk factors for coronary artery disease, previous angina episodes, absence of an allergic history, no indication of allergen exposure, typical cardiac signs and symptoms (such as chest pain on exercise) help distinguish. Severe anaphylactic reactions can trigger cardiac events.
Differentiating Tests
- Elevated cardiac enzymes (creatine kinase and troponin). ECG may show signs of myocardial ischemia (elevated ST segments or flipped T waves). Chest x-ray may show signs of congestive heart failure (e.g., pulmonary edema, changes in the cardiac silhouette).
Hypovolemic shock
Differentiating Signs/Symptoms
- Water or fluid loss occurs via heat exposure, profuse sweating, significant blood loss, vomiting, and diarrhea. Patients report thirst and a drop in urinary output. Anaphylaxis is a form of hypovolemic shock secondary to intravascular fluid shifts. Establishing an alternative cause of hypovolemia will differentiate from anaphylaxis.
Differentiating Tests
- A drop in hematocrit suggests blood loss.
- BUN/Cr >20 suggests volume depletion.
Vasovagal reaction
Differentiating Signs/Symptoms
- The characteristic feature is hypotension, with pallor, weakness, nausea, vomiting, and diaphoresis. The sudden onset, the cardiovascular collapse, and unconsciousness are all also typical of anaphylaxis.
- May be differentiated by the lack of cutaneous manifestations, the absent allergic history, and the presence of bradycardia instead of the tachycardia, even though either can be absent or misleading.
Differentiating Tests
- There is no differentiating test.
Asthma
Differentiating Signs/Symptoms
- Absence of allergen exposure, or of cutaneous or digestive findings, and a history of previous asthma episodes help differentiate. A rapid onset is suggestive of anaphylaxis and should at least trigger referral to higher-level medical care.
Differentiating Tests
- There is no differentiating test.
COPD, acute exacerbation
Differentiating Signs/Symptoms
- Absence of allergen exposure, or of cutaneous or digestive findings, and a history of established chronic lung disease help differentiate.
Differentiating Tests
- There is no differentiating test.
Hereditary angioedema
Differentiating Signs/Symptoms
- Characterized by recurrent episodes of slowly progressing angioedema of the skin, mucosa, and submucosal tissue. There is no urticaria, hypotension, or history of allergen exposure as in anaphylaxis. Family history is positive.
Differentiating Tests
- Deficiency or underactivity of the C1 esterase inhibitor enzyme.
- Serum complement C4 and CH50 are low.
Vocal cord dysfunction syndrome
Differentiating Signs/Symptoms
- Cutaneous signs, digestive findings, hypotension, and allergen exposure are not present.
Differentiating Tests
- Pharyngeal endoscopy by an ear, nose, and throat specialist will not show laryngeal edema but instead vocal cord adduction.
Foreign body aspiration
Differentiating Signs/Symptoms
- No allergen exposure, no cutaneous or digestive findings, but a history of foreign body aspiration differentiate this diagnosis.
Differentiating Tests
- Imaging and bronchoscopy are used to locate and document the foreign body. If the object inhaled is radio-opaque (e.g., a small coin), a plain radiograph of the chest may show its location.
Differentiating Signs/Symptoms
- MSG symptom complex may occur subsequent to MSG exposure. One or more of the following is present: burning sensation in the back of the neck, forearms, and chest; numbness in the back of the neck, radiating to the arms and back; tingling, warmth, and weakness in the face, temples, upper back, neck, and arms; facial pressure or tightness; chest pain; headache; nausea; rapid heartbeat; bronchospasm; drowsiness; and weakness. No urticaria, angioedema, or hypotension occurs.
Differentiating Tests
- Serum histamine levels and mast cell tryptase are not elevated.
Carcinoid syndrome
Differentiating Signs/Symptoms
- On examination, there is an associated right heart murmur.
Differentiating Tests
- Urinalysis will show high levels of hydroxy indole acetic acid.
Postmenopausal hot flashes
Differentiating Signs/Symptoms
- Hot flash appears several times a day and lasts for 4 to 5 minutes. There are no respiratory tract symptoms and no hypotension.
Differentiating Tests
- There is no differentiating test.
Differentiating Signs/Symptoms
- Usually appears within 4 to 10 minutes after the start, or soon after the completion, of a vancomycin infusion. It is characterized by flushing and/or an erythematous rash that affects the face, neck, and upper torso. Hypotension and angioedema may also occur but less frequently.
Differentiating Tests
- There is no differentiating test.
Panic disorder
Differentiating Signs/Symptoms
- In some affected people, functional stridor develops as a result of forced adduction of the vocal cords; however, there is no urticaria, angioedema, or hypotension.
Differentiating Tests
- There is no differentiating test.
Differentiating Signs/Symptoms
- Symptoms resemble IgE-mediated food allergy, but are most prominent on upper torso and face. Erythematous rash, but no urticaria noted. Resolves untreated within 12 hours.
Differentiating Tests
- Skin test to suspected seafood is negative. Histamine level in consumed fish elevated.
Criteria
- Acute onset of an illness (minutes to hours)
- Involvement of skin, mucosal tissue, or both (i.e., generalized hives, pruritus or flushing, swollen lips-tongue-uvula) and at least 1 of the following: respiratory compromise (i.e., dyspnea, wheeze-bronchospasm, stridor, reduced peak expiratory flow [PEF], hypoxemia) or reduced BP or associated symptoms of end-organ dysfunction (i.e., hypotonia/collapse, syncope, incontinence)
- Occurrence of 2 or more of the following symptoms or signs after exposure to a likely allergen (minutes or hours)
- Involvement of skin, mucosal tissue, or both (i.e., generalized hives, pruritus or flushing, swollen lips-tongue-uvula)
- Respiratory compromise (i.e., dyspnea, wheeze-bronchospasm, stridor, reduced PEF, hypoxemia)
- Reduced BP or associated symptoms of end-organ dysfunction (i.e., hypotonia/collapse, syncope, incontinence)
- Persistent gastrointestinal symptoms (i.e., crampy abdominal pain, vomiting)
- Reduced BP after exposure to a known allergen (minutes to several hours)
- Systolic BP of <90 mmHg or >30% decrease from baseline.
Treatment Approach
Cardiopulmonary arrest
Airway management
Cardiac support
Epinephrine (adrenaline)
Patients with coronary artery disease
Other treatments in acute phase
Post-emergency stabilization
Treatment of the underlying etiology - immunotherapy
Treatment Options
all patients: acute onset
cardiopulmonary assessment + supportive measures
Comments
- Patients may present with symptoms that range in severity, but cardiac collapse and respiratory compromise cause the most urgent concern. Patients presenting with milder symptoms can rapidly deteriorate and should be closely monitored.[72]
- Regardless of severity, all patients with a diagnosis of anaphylaxis should be kept under observation until signs and symptoms have fully resolved.[12]
- Unless precluded by shortness of breath or vomiting, the patient should be placed in a supine position with legs elevated (shock or Trendelenburg position). This will augment venous return, and thereby increase preload and enhance cardiac output. Studies have shown that an upright position may contribute to a fatal outcome.[82]
- Supplemental oxygen should be considered for all patients with anaphylaxis regardless of their respiratory status, and must be administered to any patient with respiratory or cardiovascular compromise and to those who do not respond to initial treatment with epinephrine (adrenaline).[72]
- Breathing should be monitored by continuous oxygen saturation or blood gas determination. Inadequate respiratory efforts may indicate the need for ventilatory support.
IM epinephrine (adrenaline)
Primary Options
- epinephrine (adrenaline)
children: 0.01 mg/kg (as a 1:1000 solution) intramuscularly every 5-15 minutes, maximum 0.3 mg/dose; adults: 0.3 to 0.5 mg (as a 1:1000 solution) intramuscularly every 5-15 minutes
- epinephrine (adrenaline)
Comments
- Immediate administration of adequate doses of epinephrine will decrease patient mortality and morbidity.[24] All patients with signs of a systemic reaction, especially hypotension, airway swelling, or difficulty breathing, should receive immediate intramuscular (IM) epinephrine in the anterolateral thigh.[83] [84] [85] [86] [87] [88]
- A prescription for two epinephrine auto-injectors must be given after any episode of anaphylaxis.[72] [93] The patient or caregiver should carry both at all times and be familiar with their use.[85] For children at risk of anaphylaxis, the epinephrine auto-injectors should be prescribed in conjunction with a personalized written emergency plan.[85] [94] American Academy of Pediatrics: allergy and anaphylaxis emergency plan
assess & secure airway
Comments
- As even minor airway compromise can quickly progress to complete airway occlusion, immediate airway assessment and support is critical. If possible, airway assessment and management should be performed by a skilled anesthesiologist or emergency physician. Early prophylactic intubation or even cricothyrotomy may be necessary, especially if there is inspiratory stridor.[72] Inadequate respiratory efforts may indicate the need for ventilatory support.
intravenous normal saline
Comments
- Aggressive intravenous fluid replacement is indicated due to the intravascular volume redistribution into venous capacitance vessels and the interstitial tissue. The human vascular system consists of a high-pressure small-volume arterial system and a large low-pressure venous reservoir that expands in anaphylaxis, absorbing much of the circulating blood volume.
cardiopulmonary arrest
CPR + intravenous epinephrine
Primary Options
- epinephrine (adrenaline)
children: 0.01 mg/kg (as a 1:10,000 solution) intravenously every 3-5 minutes, maximum 1 mg/dose; adults: 1 mg (as a 1:10,000 solution) intravenously every 3-5 minutes
- epinephrine (adrenaline)
Comments
- If no pulse or breathing is present, CPR and advanced cardiac life support measures with intubation and ventilation are indicated.
- High-dose intravenous epinephrine is given.[72]
severe hypotension
intravenous epinephrine
Primary Options
- epinephrine (adrenaline)
children: 0.01 mg/kg (as a 1:10,000 solution) intravenously every 5 minutes, maximum 0.3 mg/dose; adults: 0.1 mg (as a 1:10,000 solution) intravenously every 5 minutes
- epinephrine (adrenaline)
Comments
- Continuous intravenous infusion of epinephrine, titrated to effect, is reserved for experienced practitioners. No intravenous dose regimen is universally recognized.
intravenous glucagon
Primary Options
- glucagon
children: consult specialist for guidance on dose; adults: 5 mg intravenously initially, may repeat in 10-15 min if no response, followed by 5-15 micrograms/min if response seen
- glucagon
Comments
- In patients prescribed beta-blockers for coronary artery disease (CAD), both the medication and the underlying comorbidity complicate the treatment of severe anaphylaxis. The beta-blocker counteracts epinephrine by limiting heart rate and compromising cardiac output. CAD limits cardiac reserve, which might compound the hypotension occurring due to the release of vasoactive mediators. The stresses of hypotension, tachycardia, and endogenous or iatrogenic adrenergic agents may cause myocardial ischemia by reducing perfusion during diastole. Glucagon may be used to overcome beta blockade, but the resulting tachycardia can be detrimental in patients with severe CAD.[6] Therefore, early consultation of a cardiologist is warranted.
persistent respiratory symptoms
inhaled beta-2 agonist
Primary Options
- albuterol inhaled
children: 0.15 mg/kg nebulized every 20 minutes for 3 doses, then 0.15 to 0.3 mg/kg every 1-4 hours when required; adults: 1.25 to 5 mg nebulized every 20 minutes for 3 doses, then every 1-4 hours when required
- albuterol inhaled
Comments
- Persistent respiratory symptoms after the administration of epinephrine may benefit from inhaled beta-2 agonists.[72]
- The beta-2 agonist also has crossover activity at the beta-1 receptor and may therefore cause tachycardia and hypertension. Repeat dosing is limited by these adverse effects.
symptomatic hives and rhinorrhea
H1 antagonist + H2 antagonist
Primary Options
- diphenhydramine
children: 1-2 mg/kg intravenously/intramuscularly; adults: 25-50 mg intravenously/intramuscularly
and
- cimetidine
children: consult specialist for guidance on dose; adults: 300 mg intravenously as a single dose
- diphenhydramine
Comments
- Use of H1 and H2 antagonists is limited to relief of itching, hives, and rhinorrhea. Their use should never delay or replace the use of intramuscular epinephrine.[95] [96] [97] Most antihistamines can be given intravenously, intramuscularly, or orally. In perioperative anaphylaxis, no evidence for harm in the administration of antihistamines was reported in a large UK audit.[28] Oral administration may be sufficient for very mild allergic reactions but not anaphylaxis.
post-emergency stabilization
corticosteroids
Primary Options
- methylprednisolone
children and adults: 1-2 mg/kg/day intravenously
- methylprednisolone
- prednisone
children and adults: 0.5 to 1 mg/kg/day orally
- prednisone
Comments
- Corticosteroids may be prescribed as adjunctive therapy after the administration of epinephrine.[1] [12] Corticosteroids may decrease the risk of symptoms associated with anaphylaxis, including urticaria. Guidelines published in 2020 advise against administering corticosteroids to prevent biphasic anaphylaxis. This is based on limited evidence suggesting that there is no clear benefit in terms of risk reduction.[12]
- Corticosteroids, orally or intravenously, have no role in the acute management of anaphylaxis; they have a slow onset of action and may have no effect for 4 to 6 hours.[73]
patients with identified allergen
immunotherapy
Comments
- Subcutaneous venom immunotherapy is recommended for prevention of systemic reactions in patients with a history of anaphylaxis subsequent to insect sting.[72] [92] The treatment is highly effective at preventing these systemic reactions (80%-98%).[72] Venom immunotherapy increases the risk of adverse systemic reactions during treatment.[98] Most patients can discontinue venom immunotherapy after 5 years with modest residual risk of a severe sting reaction (<5%).[72]
- Avoidance of food allergens remains the preventive mainstay of food-induced anaphylaxis.[72] Subcutaneous, oral, and sublingual immunotherapy routes have been assessed. Studies suggest that while treatment may lead to desensitization, few patients attain tolerance.[72] Food-allergy-specific immunotherapy remains investigational;[72] it is associated with adverse reactions, including anaphylaxis, and is not recommended for routine clinical use.[99]
- Drug desensitization may be considered to induce temporary drug tolerance in patients with immunoglobulin E-mediated drug-induced anaphylaxis who require the causal drug, and where there is no effective alternative option.[72] [92] Drug desensitization should be performed by experienced clinicians in an appropriate setting.
Emerging Tx
New forms of immunotherapy administration
Peptide immunotherapy
Recombinant food proteins
Immunostimulatory sequences (ISS)
Humanized monoclonal anti-IgE
Traditional Chinese medicine (TCM)
Blockade of vasoactive mediators
Prevention
Primary Prevention
Secondary Prevention
Follow-Up Overview
Prognosis
Moderate anaphylaxis
Cardiac arrest due to anaphylaxis
Monitoring
Complications
Citations
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Key Articles
Other Online Resources
Referenced Articles
Guidelines
Diagnostic
Summary
Guidelines on the evaluation of a patient with a history of anaphylaxis.Published by
American Academy of Allergy, Asthma & Immunology; American College of Allergy, Asthma & Immunology
Published
2020
Summary
This practice parameter seeks to refine guidelines for the diagnosis of stinging insect hypersensitivity.Published by
American Academy of Allergy, Asthma & Immunology; American College of Allergy, Asthma & Immunology
Published
2016
Summary
Guidelines on the evaluation of a patient with a history of anaphylaxis.Published by
American Academy of Allergy, Asthma & Immunology; American College of Allergy, Asthma & Immunology
Published
2015
Summary
Consensus guideline that addresses diagnosis of immunoglobulin E (IgE)-mediated and non-IgE-mediated reactions to food.Published by
National Institute of Allergy and Infectious Disease
Published
2010
Summary
Discusses the current utility and validity of diagnostic tests for allergy.Published by
American Academy of Allergy, Asthma & Immunology; American College of Allergy, Asthma & Immunology
Published
2008
Summary
Evidence-based guidance on the care of adults, young people, and children following emergency treatment for suspected anaphylaxis.Published by
National Institute for Health and Care Excellence (UK)
Published
2020
Summary
This summary covers the diagnosis, treatment, investigation, and follow-up of patients with anaphylactic reactions.Published by
Resuscitation Council (UK)
Published
2021
Summary
This guideline provides a comprehensive overview of the diagnosis and assessment of food allergy in children and young people.Published by
National Institute for Health and Care Excellence (UK)
Published
2011 (reaffirmed 2018)
Treatment
Summary
Guidelines on the management of a patient with a history of anaphylaxis.Published by
American Academy of Allergy, Asthma & Immunology; American College of Allergy, Asthma & Immunology
Published
2020
Summary
Recommendations on the prevention of peanut allergy in infants at various risk levels.Published by
National Institute of Allergy and Infectious Diseases
Published
2017
Summary
Information to help healthcare professionals complete a written emergency plan for children at risk of anaphylaxis.Published by
American Academy of Pediatrics
Published
2017
Summary
Seeks to refine guidelines for the management of stinging insect hypersensitivity, with particular emphasis on the appropriate use of immunotherapy.Published by
American Academy of Allergy, Asthma & Immunology; American College of Allergy, Asthma & Immunology
Published
2016
Summary
Comprehensive guidelines on the management of anaphylaxis.Published by
American Academy of Allergy, Asthma & Immunology; American College of Allergy, Asthma & Immunology
Published
2015
Summary
Provides brief guidance on emergency treatment of anaphylaxis.Published by
American Heart Association
Published
2015
Summary
This summary covers the diagnosis, treatment, investigation, and follow-up of patients with anaphylactic reactions.Published by
Resuscitation Council (UK)
Published
2021
Summary
Updated guidelines for clinical practice. The members of the European Network for Drug Allergy approved the guidelines.Published by
French Society for Anaesthesia and Intensive Care (Societe Francaise d'Anesthesie et de Reanimation); French Society of Allergology (Societe Francaise d'Allergologie)
Published
2011