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. It should be administered early to prevent progression to life-threatening hemodynamic and respiratory collapse. Anaphylaxic reactions are variable, and it is not possible to predict the severity, rapidity of progression, or resolution at the onset of an episode. Although NEJM Resident 360 generally does not include dosages, epinephrine dosing is provided given the urgency of administration.

• Epinephrine dosing: Instructions for administering epinephrine in the event of an anaphylactic reaction are as follows:

  • Adults: 0.3 to 0.5 mg intramuscularly (IM) in the mid-outer thigh using a 1:1000 (1.0 mg/mL) concentration. Subcutaneous administration should not be used. If response is inadequate or lacking, can repeat the epinephrine in 5-15 minutes. Beta-blockers may decrease efficacy of epinephrine and require additional epinephrine or glucagon to bypass the beta-adrenergic receptor and directly activate adenyl cyclase.

  • Children: 0.01 mg/kg (maximum dose of 0.3-0.5 mg) intramuscularly (IM) using a 1:1000 (1.0 mg/mL) concentration. Subcutaneous administration should not be used.

  • Auto-injecting devices are available as 0.1, 0.15, and 0.3 mg.

• 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: These medications may be considered for the secondary treatment of anaphylaxis. For example, antihistamines may 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 systemic reaction to a stinging insect should be referred to an allergy-immunology specialist for venom skin testing.

• Venom allergy testing is generally not indicated if reactions are 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 systemic or anaphylactic reactions should carry injectable epinephrine until allergy evaluation.

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

• If the anaphylactic reaction is followed by a positive test result for venom-specific IgE, either on skin testing or in vitro testing, venom immunotherapy (VIT) can be considered. VIT has been shown to decrease the risk of subsequent anaphylaxis from a future sting from 50% to <5%.

  • The number needed to treat is 2 for VIT in an adult patient with a history of anaphylaxis to stinging insects and positive skin tests.

• For patients with severe reactions to hymenoptera stings, consider obtaining a tryptase level to evaluate for underlying mastocytosis.

Immediate Hypersensitivity Reactions to Radiocontrast Media

Adverse reactions to radiocontrast media can be divided into the following types of reactions:

• Chemotoxic reactions (physiologic reactions) are related to the chemical properties of the contrast and are dependent on the dose and the infusion rate.

• Hypersensitivity reactions are considered to be idiosyncratic and independent of dose and infusion rate.

  • The majority of immediate hypersensitivity reactions to radiocontrast media are thought to be non-IgE-mediated, with only a small percentage of reactions involving IgE.

  • The non-IgE-mediated mechanisms for immediate hypersensitivity reactions to radiocontrast media include direct mast-cell activation; activation of the coagulation, kinin, and complement cascades; inhibition of platelet aggregation; increased serotonin release; and inhibition of enzymes including cholinesterase.

Treatment of Hypersensitivity Reactions to Radiocontrast Media

Premedication regimens: Although the 2020 Joint Task Force Practice Parameter Update on anaphylaxis does not recommend premedication for patients with a history of immediate allergic reaction to radiocontrast media who subsequently receive low or iso-osmolar contrast material, evidence is lacking and the recommendation is in conflict with that of the American College of Radiology. Therefore, it is at the discretion of providers to determine if premedication is indicated. The following are common premedication regimens for patients with hypersensitivity reactions to contrast:

• Oral prednisone at 13 hours, 7 hours, and 1 hour before the procedure (use IV methylprednisolone if oral administration is not feasible) and/or diphenhydramine (oral or IV) 1 hour before the procedure (use cetirizine if diphenhydramine cannot be used).

Rapid pretreatment: In patients requiring an urgent or emergent procedure, the following rapid pretreatment protocol can be used:

• methylprednisolone (40 mg IV) immediately and every 4-5 hours until completion of procedure and

• diphenhydramine (oral, IV, or IM) 1 hour before radiocontrast media administration and

• the lowest-osmolar radiocontrast media agent available

Severe reactions to contrast are treated in the same way as anaphylactic reactions, with epinephrine as the first-line therapy.