Content – Anaphylaxis

Introduction

Anaphylaxis is a potentially fatal, systemic allergic reaction with an acute onset. Prompt recognition and treatment greatly reduces its mortality. As a clinician, anaphylaxis provides an excellent opportunity for life saving interventions.

Causes and Risk Factors

There are many potential causes of anaphylaxis; any allergen can evoke an anaphylactic response in a previously sensitized individual. Allergens are most commonly ingested orally, though inhalation (not simply smelling) is also a possible route of entry. Rarely, skin contact can cause anaphylaxis.

Food allergens are the most common cause in children, while medication (especially penicillin) and insect stings (ie Hymenoptera) predominate in adults (Sampson et al, 1992).

Fire ants, in the southern US and Central/South America, can cause anaphylaxis. Spider bites do NOT cause anaphylaxis.

A major risk factor for anaphylaxis is a previous anaphylactic episode; however, size of previous reaction does not relate to increased risk.

Risk factors that increase the chance of death include asthma and cardiovascular disease. Other respiratory conditions such as chronic obstructive pulmonary disease also increase the risk of death.

Pathophysiology

Anaphylaxis is typically an immediate hypersensitivity reaction causing the release of immunoglobulin E (IgE). Autoimmune and non immune mechanisms can also be involved, although to a much lesser extent.

Signs and Symptoms

Anaphylaxis onsets in minutes to hours of an inciting event, though a biphasic presentation can result in the recurrence of symptoms 8-72 hours after initial resolution following treatment. Occasionally, protracted anaphylaxis can last for hours to days.

Anaphylaxis is highly likely when any one of the following 3 criteria are fulfilled, over minutes-hours: (Sampson et al, 2006)

1. Acute onset of an illness with involvement of the skin, mucosal tissue, or both and at least one of the following:

1. respiratory compromise
2. reduced BP or associated symptoms of end-organ dysfunction (eg, hypotonia [collapse], syncope, incontinence

2. Two or more of the following that occur rapidly after exposure to a likely allergen for that patient:

1. involvement of the skin-mucosal tissue
2. respiratory compromise
3. reduced BP or associated symptoms
4. persistent gastrointestinal symptoms

3. reduced BP after exposure to known allergen for that patient:

1. Infants and 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

Specific signs and symptoms can include:

Investigations

No investigations are needed for the diagnosis and management of anaphylaxis, though a full laboratory assessment is normally done in order to rule out other conditions, as are described below.

Respiratory and cardiovascular monitoring are an important part of anaphylaxis management.

Differential Diagnosis

The differential diagnosis of anaphylaxis includes many conditions, both benign and life threatening. The benign causes include:

• vasovagal reaction
• alcohol consumption
• anxiety
• generalized urticaria
• Menopausal hot flashes

Potentially fatal conditions include:

• other forms of shock
• myocardial infarction
• stroke
• angioedema
• asthma exacerbation
• vocal cord dysfunction
• other causes of respiratory distress (Lieberman et al, 2009).

Treatments

Treatment should be given without delay, given the life-threatening nature of anaphylaxis. Elements of treatment include:

• call for help
• remove the suspected antigen
• place the patient in a supine position and provide reassurance
• maintain the airway, breathing, and circulation; begin CPR if needed
• administer supplemental oxygen
• administer intramuscular or intravenous epinephrine, recording the time given
• volume resuscitate as needed (normal saline preferred)

Epinephrine is the pharmacological intervention of choice, given IM every 5-15 minutes. The injection should be given in the mid-anterolateral thigh, into the vastus lateralis muscle. In patients with severe hypotension or cardiac arrest, intravenous infusion of epinephrine may be necessary (see vasopressors and inotropes).

There are no absolute contraindications to the use of epinephrine in the treatment of anaphylaxis. Patients with cardiac disease are at increased risk with the use of epinephrine, however the risks of delaying treatment outweigh the benefits.

Other medications to consider include:

• antihistamines (eg diphenydramine, cetirizine) for symptomatic treatment of hives and itch
• ranitidine for gastrointestinal upset
• bronchodilators
• glucocorticoids (take 1 h to work)

Patients who are on beta-blocker therapy may be resistant to epinephrine treatment, with refractory bradycardia and hypotension. In these patients, glucagon must be administered as an adjuvant to epinephrine, with an intravenous bolus given.

If patients have a rapid response, they may be discharged after 8-10 hours. If, however, their symptoms are moderate or severe, they should be admitted.

Patients should be provided with an written anaphylaxis emergency plan and an epinephrine pen on discharge. If etiology is unclear, allergy testing may be warranted. An allergy bracelet may be worn to advise others of the allergy.

Consequences and Course

Anaphylaxis can rapidly be fatal:

• iatrogenic: 5 min
• stings: 15 min
• food: 30 min

If promptly recognized and treated, anaphylaxis has no long term sequelae. A delay in the recognition and treatment can result in death. For this reason, clinicians should begin treatment with epinephrine as soon as anaphylaxis is suspected. Patients who have had an anaphylactic reaction are at increased risk of having another episode if exposed to the same antigen.

Resources and References

Sampson HA, Mendelson LM, Rosen JP. Fatal and near-fatal anaphylactic reactions to food in children and adolescents. N Engl J Med. 1992;327:380-384.

Sheikh A, Shehata YA, Brown SGA, Simons FER. Adrenaline (epinephrine) for the treatment of anaphylaxis with and without shock. Cochrane Database of Systematic Reviews 2008, Issue 4. Art. No.: CD006312. DOI: 10.1002/14651858.CD006312.pub2.

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. Sampson HA, Muñoz-Furlong A, Campbell RL, Adkinson NF Jr, Bock SA, Branum A, Brown SG, Camargo CA Jr, Cydulka R, Galli SJ, Gidudu J, Gruchalla RS, Harlor AD Jr, Hepner DL, Lewis LM, Lieberman PL, Metcalfe DD, O’Connor R, Muraro A, Rudman A, Schmitt C, Scherrer D, Simons FE, Thomas S, Wood JP, Decker WW. Ann Emerg Med. 2006 Apr;47(4):373-80.

Lieberman, PL. Anaphylaxis. In: Middleton’s Allergy Principles & Practice, Adkinson, NF Jr, Bochner, BS, Busse, WW, et al (Eds), 7th ed, St Louis 2009. p.1027.

Topic Development

July 2010, Caleb Zelenietz