Anaphylaxis

Anaphylaxis is defined as a serious allergic or hypersensitivity reaction that is rapid in onset and may be life-threatening. Anaphylaxis can be classified into immunologic (immunoglobulin E [IgE]- or non-IgE-mediated), nonimmunologic, or idiopathic as follows:

• Type I, immediate, IgE-mediated reaction can be triggered by medications, food, hymenoptera (hornet, bee, or wasp) stings, or latex.

• Non-IgE-mediated reaction can be caused by radiographic contrast material and nonsteroidal anti-inflammatory drugs (NSAIDs), among other sources.

• Nonimmunologic anaphylaxis can stem from exercise, swings in temperature, other medications, alcohol, or idiopathic origins.

The following figure summarizes the mechanisms and triggers of anaphylaxis.

(Source: World Allergy Organization Guidelines for the Assessment and Management of Anaphylaxis. World Allergy Organ J 2011.)

Diagnosis

Any one of three definitions for anaphylaxis outlined in the following figure can be used to make a diagnosis, depending on the clinical presentation.

(Source: Anaphylaxis - A 2020 Practice Parameter Update, Systematic Review, and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Analysis. J Allergy Clin Immunol 2020.)

Management

Epinephrine is the first-line medication for treatment of anaphylaxis and should be administered intramuscularly early to prevent progression to life-threatening hemodynamic and respiratory collapse. Anaphylaxis is variable, and it is not possible to predict the severity, rapidity of progression, or resolution at the onset of an episode of anaphylaxis. No absolute contraindications exist for using epinephrine. Although NEJM Resident 360 generally does not include dosages, epinephrine dosing is provided given the urgency of administration.

• Epinephrine dosing: Dosing instructions for administering epinephrine in the event of anaphylaxis are as follows:

  • Children: 01 mg/kg (maximum dose of 0.3-0.5 mg) injected intramuscularly (IM) in the mid-outer thigh using a 1.0 mg/mL concentration (the ratio expression of 1:1000 is equivalent to 1.0 mg/mL). Auto-injecting devices are available as 0.1, 0.15, and 0.3 mg. Subcutaneous administration should not be used. For children weighing >50 kg, the maximum dose is 0.5 mg. If there is an inadequate or lack of response, epinephrine administration can be repeated in 5-15 minutes.

• Early recognition and management of anaphylaxis is critical, as signs and symptoms can progress quickly and result in severe morbidity and mortality.

• Prompt administration of epinephrine is the cornerstone of treatment for anaphylaxis. The following steps should be considered immediately in the management of anaphylaxis:

  • removal of inciting agent

  • calling for help

  • intramuscular injection of epinephrine at earliest opportunity

  • placement of patient in supine position with lower extremities elevated

  • provision of supplemental oxygen

  • volume resuscitation with intravenous (IV) fluids

• Biphasic anaphylaxis is defined as a recurrence of symptoms that develop following the apparent resolution of the initial anaphylactic episode with no additional exposure to the causative agent. More-severe initial presentation, delayed administration of epinephrine, and repeated doses of epinephrine are associated with biphasic anaphylaxis. Given this risk, patients should go to the emergency department for monitoring if epinephrine is administered outside the hospital.

Antihistamines and glucocorticoids may be considered for the secondary treatment of anaphylaxis. For example, antihistamines can be used to relieve itching and urticaria and glucocorticoids may be indicated in patients with asthma. However, if used prior to epinephrine, antihistamines and glucocorticoids may delay administration of first-line treatment, potentially resulting in a more-severe reaction. Further, antihistamines and glucocorticoids have not been shown to prevent biphasic anaphylaxis.

Venom Hypersensitivity

Patients with a history of anaphylaxis or a systemic reaction to a stinging insect should be referred to an allergy-immunology specialist for skin testing to venoms.

• In both children and adults, a severe systemic/anaphylactic reaction to a suspected hymenoptera insect makes the patient a candidate for venom allergy testing. Measurement of baseline serum tryptase can also be considered.

• Patients with systemic or anaphylactic reactions should carry injectable epinephrine until allergy evaluation.

• Venom allergy testing is generally not indicated if reactions were limited to the skin (e.g., urticaria and localized angioedema) but may be considered in special circumstances, including patients with high-risk factors such as frequent exposure and cardiovascular or respiratory conditions.

• Patients with symptoms limited to the skin have only a 10% chanceof a future systemic reaction, and the majority of these are only cutaneous reactions.

• In patients with a systemic/anaphylactic and subsequent positive skin testing and/or specific IgE laboratory testing, venom immunotherapy reduces the risk of systemic reaction with an efficacy of up to 98%. In one study, children with a moderate-to-severe anaphylactic reaction to hymenoptera stings had a higher rate of reaction on subsequent stings if the patient did not receive venom immunotherapy (32% vs. 5% in patients who had received venom immunotherapy).

For more information on anaphylaxis, see Respiratory Distress in the Pediatric Emergency Medicine rotation guide.