I. Problem/Condition.

Anaphylaxis is a severe allergic reaction that is acute and potentially fatal. It is a clinical diagnosis that requires prompt identification and management.

As the presentation is variable, three clinical criteria have been established to aid in diagnosis. Any patient meeting one of these would be defined as having anaphylaxis:

  • The acute onset of a reaction (minutes to hours) involving the skin, mucosal tissue, or both, and at least one of the following: respiratory compromise, reduced blood pressure (BP), or symptoms of end-organ dysfunction.
  • Two or more of the following that occur rapidly after exposure to a potential allergen, including involvement of the skin/mucosal tissue, respiratory compromise, reduced BP or associated symptoms, and/or persistent gastrointestinal symptoms.
  • Reduced BP after exposure to a known allergen (minutes to hours).

II. Diagnostic Approach

A. What is the differential diagnosis for this problem?

As anaphylaxis is a systemic reaction, it by definition can involve multiple organ systems. Thus, when faced with the possibility of anaphylaxis, there are multiple other alternative diagnoses that should also be considered.

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Pulmonary causes
  • Asthma exacerbation
  • Pulmonary embolism
  • Foreign body in lung
  • Stridor
  • Vocal cord dysfunction
  • Angioedema (hereditary or medication-induced)
Cardiac causes
  • Syncope/presyncope
  • Myocardial infarction
  • Arrhythmias
Gastrointestinal causes
  • Food poisoning
Dermatologic causes
  • Hives
  • Urticaria
  • Systemic mastocytosis

B. Describe a diagnostic approach/method to the patient with this problem

The key to approaching a patient with suspected anaphylaxis is performing a rapid assessment including key historical points that will aid in narrowing your differential, along with a physical exam that identifies potential areas of involvement.

1. Historical information important in the diagnosis of this problem.

When inquiring into the possibility of anaphylaxis, there are essential components needed to aid in the diagnosis:

  • Any potential allergen exposure, including timing/duration of exposure.
  • Presence of any cutaneous manifestations.
  • Any signs of airway obstruction (upper/lower airway).
  • Any syncope or presyncopal symptoms.
  • Presence of gastrointestinal symptoms.
  • Any treatment given prior to presentation.
  • Recurrence of symptoms after remission (if currently in remission).
  • Prior history of anaphylaxis.

Identifying specific patient populations that are at higher risk for anaphylaxis is also important:

  • Teenagers/young adults are at increased risk for food-allergen induced anaphylaxis.
  • Patients with asthma and/or cardiovascular disease are at increased risk of mortality in anaphylaxis.
  • Elderly patients are at increased risk due to other comorbidities (e.g. chronic obstructive pulmonary disease (COPD), coronary artery disease) that may complicate the clinical presentation.
  • Certain medications that a patient is taking may confound the presentation and impede prompt recognition of anaphylaxis (e.g. beta-blockers, antihistamines).
  • Patients experiencing symptoms quickly after exposure (within 30 minutes) are more likely to have a severe reaction.

2. Physical Examination maneuvers that are likely to be useful in diagnosing the cause of this problem.

There are no specific maneuvers that aid in the diagnosis of anaphylaxis. It is through recognition of the involvement of certain organ systems that aids in the diagnosis.

Anaphylaxis will affect two or more of five major organ systems:

  • Flushing
  • Pruritus
  • Urticaria
  • Angioedema
  • Congestion
  • Hoarseness
  • Stridor
  • Dyspnea
  • Wheezing
  • Nausea
  • Vomiting
  • Abdominal pain/cramping
  • Oral pruritus
  • Tachycardia/bradycardia or other arrhythmia
  • Hypotension
  • Syncope
  • Chest pain
  • Headache
  • Confusion
  • Irritability
  • Dizziness

Of these, pulmonary and cutaneous manifestations are the most common seen in patients with anaphylaxis.

3. Laboratory, radiographic and other tests that are likely to be useful in diagnosing the cause of this problem.

Given the wide spectrum of the differential in the diagnosis of anaphylaxis, there has been further inquiry into possible laboratory studies that would assist in confirming the diagnosis. The most widely recommended test is the serum tryptase. Peak levels of serum tryptase are found within 2 hours of exposure, and have been found to persist up to 6 hours or longer.

Other tests to assist in narrowing the differential include:

Laboratory studies
  • Plasma histamine levels may be utilized when anaphylaxis occurs in the hospital setting. Blood sample should be obtained within one hour.
  • Complete blood count (CBC), cardiac enzymes (creatine kinase (CK), troponin), D-dimer
  • Chest x-ray (evaluate for stridor, foreign body, pneumothorax)
  • Computed tomography (scan) (rule out pulmonary embolism (PE))
  • Electrocardiogram (ECG) (rule out myocardial infarction (MI), arrhythmia)

C. Criteria for Diagnosing Each Diagnosis in the Method Above.


D. Over-utilized or “wasted” diagnostic tests associated with the evaluation of this problem.

While there are no over-utilized tests in the diagnosis of anaphylaxis, the important principle is that testing should not delay treatment when there is suspicion of anaphylaxis.

Tryptase levels may help in confirming a diagnosis, but anaphylaxis is a clinical diagnosis. As such, a tryptase level may not always be readily available and is not necessary to initiate prompt treatment.

III. Management while the Diagnostic Process is Proceeding

A. Management of anaphylaxis.

While obtaining a thorough history and performing a physical exam is important, time is of the essence if anaphylaxis is suspected. Therefore, the clinician must act quickly in initiating measures to stabilize the patient who may be clinically unstable at time of presentation.

Airways, breathing and circulation
  • The patient’s airway should be determined to be adequate, with preparations for establishing/maintaining an airway in case of respiratory compromise.
  • During physical examination, the patient’s breathing pattern should be evaluated and monitored as an indicator of possible progression of symptoms.
  • Evaluation of the patient’s circulatory status (heart rate, BP, perfusion) is also important, as it will also assist in determining next steps in management.
Intravenous, oxygen, monitor
  • Obtain adequate intravenous (IV) access (2 large-bore, 16/18 gauge if possible), as the need for crystalloids or even vasopressor therapy may arise in a patient who may be or will become hemodynamically unstable. Fluid therapy should be initiated immediately in hypotensive patients as massive fluid shifts may occur in anaphylaxis.
  • Supplemental O2 should be placed supportively in case of respiratory distress, keeping SpO2 greater than 92%.
  • Continuous cardiopulmonary monitoring is essential to stay apprised of the patient’s clinical status; it may also provide insight on potential alternative diagnoses (e.g. arrhythmia).

When anaphylaxis is suspected, the first-line of treatment in all patients is epinephrine. This should be given first, with continuous monitoring of the patient to determine if further dosing is indicated.

While there are alternative methods of administration, intramuscular (IM) is preferred over subcutaneous (SQ) injection, associated with higher plasma concentration levels and improved survival. Meanwhile, IV formulations are associated with tachyarrhythmia and myocardial infarction, so are mainly used if the patient is found to be in shock.

The recommended dose for adults is 0.3-0.5 mg per single dose (1 mg per ml) injected intramuscularly into the mid-outer thigh. Caution must be utilized to ensure using the correct epinephrine dilution.

If the patient has reportedly received an autoinjector of epinephrine (e.g. EpiPen®), this should not prohibit repeated therapy, especially if the patient is still exhibiting symptoms. In fact, up to 40% of patients may require an additional dose of epinephrine.


Despite lack of any randomized, controlled trials to support the use of antihistamines in anaphylaxis, they are commonly used as adjunctive therapy. They mainly alleviate skin symptoms especially when a combination of H1 (e.g., diphenhydramine) and H2 (e.g., ranitidine) blockers are used.

– Diphenhydramine IV/IM/ per os (PO): 25-50mg (adults), 1.25mg/kg (pediatric) per dose

– Ranitidine IV/PO: 50mg IV/150mg PO (adults), 1.25mg/kg IV or 2mg/kg PO (pediatric) per dose


While there is a lack of any randomized, controlled studies demonstrating effectiveness of corticosteroids, they are commonly used to prevent biphasic anaphylaxis.

– Methylprednisolone (IV) daily dose: 125mg (adults), 1mg/kg up to 60mg (pediatric)

– Prednisone (PO) daily dose: 50mg (adults), 1mg/kg up to 60mg (pediatric)

Steroids should be stopped after one or two days without a taper.

Beta 2-agonists

Use of inhaled beta-2 agonist bronchodilators (e.g., albuterol) is recommended in all patients exhibiting evidence of bronchospasm, especially with a history of pulmonary disease (asthma, COPD). Continuous monitoring (using a cardiopulmonary monitor and pulmonary exam reassessment) of the patient’s response to treatment will determine if further bronchodilator therapy is indicated.

– Albuterol (inhaled): 10-15mg/hour by continuous nebulization (adults), 0.5mg/kg/hour by continuous nebulization, up to adult dose (pediatric).

– IM Dosing: 1:1000 dilution, 0.3-0.5ml (adults), 0.01ml/kg, up to 0.3ml (children)

– Can be repeated every 5-15 minutes as needed

– 20-40% of patients may require an additional dose, patients should be observed for a minimum of 4-6 hours after symptom resolution.

B. Common Pitfalls and Side-Effects of Management of this Clinical Problem

Management points not to be missed

While pulmonary and cutaneous manifestations are most common in anaphylaxis, it is noteworthy that up to 20% of cases may not have cutaneous findings. This is important to consider when a patient may have other findings suggestive of an anaphylactic reaction and should not deter the clinician from empirically treating while obtaining more data in confirming the diagnosis.

Patients found to have anaphylaxis and appropriately treated on presentation should be observed, ideally for at least 4-6 hours after the patient is symptom-free. The reasoning for this is the risk of a biphasic anaphylactic reaction can occur in up to 20% of patients leading to a potentially worse reaction, especially if the patient has already been discharged.

Side effects of medications

Epinephrine is the mainstay of treatment in anaphylaxis. However, it does have side effects (elevation of BP, tachycardia) that cause providers to take pause prior to initiating therapy. However, the benefits of epinephrine therapy outweigh the risks. Delayed use (within 30 minutes) of epinephrine in anaphylaxis is associated with poor outcomes, including mortality. There are no contraindications to the administration of epinephrine in anaphylaxis.

Tricyclic antidepressants and monoamine oxidase inhibitors can potentiate the effect of epinephrine, and therefore contribute to an increased risk of cardiac arrhythmia. Cocaine sensitizes the heart to catecholamines and thereby potentiates the effects of epinephrine. If a patient’s history includes active use of these substances, closer monitoring should be initiated.

Beta-blockers may actually inhibit the benefits of epinephrine therapy, while also causing unopposed alpha stimulation, leading to hypertension and tachycardia. Glucagon administration is useful in those patients (dose: 1-5 mg in adults, IV over 5 minutes).

IV. What’s the evidence?

Lieberman, P, Nicklas, RA, Oppenheimer, J. “The diagnosis and management of anaphylaxis practice parameter: 2010 update”. J Allergy Clin Immunol. vol. 126. 2010. pp. 477-480.

Lieberman, P, Kemp, SF, Oppenheimer, J. “The diagnosis and management of anaphylaxis: an updated practice parameter”. J Allergy Clin Immunol. vol. 15. 2005. pp. S483-S523.

Terr, AI. “Anaphylaxis”. Clin Rev Allergy. vol. 3. 1985. pp. 3-23.

Simons, FE. “Anaphylaxis”. J Allergy Clin Immunol. vol. 125. 2010. pp. S161-S181.

Enrique, E, Garcia-Ortega, P, Sotorra, O. “Usefulness of UniCAP- tryptase fluoroimmunoassay in the diagnosis of anaphylaxis”. Allergy. vol. 54. 1999. pp. 602-6.

Ellis, AK, Day, JH. “Diagnosis and management of anaphylaxis”. CMAJ. vol. 169. 2003. pp. 307-312.

Simons, FE, Ardusso, LR, Bilò, BM. “World Allergy Organization Guidelines for the Assessment and Management of Anaphylaxis”. World Allergy Organ J. vol. 4. 2011. pp. 13-37.

Kelso, JM. “A second dose of epinephrine for anaphylaxis: How often needed and how to carry”. J Allergy Clin Immunol. vol. 117. 2006. pp. 464-564.

Sheikh, A, Ten Broek, V, Brown, SG, Simons, FE. “H1-antihistamines for the treatment of anaphylaxis: Cochrane systematic review”. Allergy. vol. 62. 2007. pp. 830

Lin, RY, Curry, A, Pesola, GR. “Improved outcomes in patients with acute allergic syndromes who are treated with combined H1 and H2 antagonists”. Ann Emerg Med. vol. 36. 2000. pp. 462

Choo, KJ, Simons, FE, Sheikh, A. “Glucocorticoids for the treatment of anaphylaxis”. Cochrane Database Syst Rev. vol. 4. 2012. pp. CD007596