Chapter 6. Anaphylaxis, Acute Allergic Reactions, and Angioedema

Allergic reactions range from localized urticaria to life-threatening anaphylaxis. Anaphylaxis refers to the most severe form of immediate hypersensitivity reaction and encompasses both IgE-mediated reactions and anaphylactoid reactions, which do not require a previous sensitizing exposure.

Anaphylaxis may occur within seconds or be delayed over an hour after an exposure; more rapid reactions are associated with higher mortality. Common exposures are foods, medications, insect stings, and allergen immunotherapy injections. Many cases are idiopathic. Criteria for anaphylaxis describe an acute progression of organ system involvement that may lead to cardiovascular collapse. Organ system involvement can include dermatologic (pruritus, flushing, urticaria, erythema multiforme, angioedema), respiratory tract (dyspnea, wheezing, cough, stridor, rhinorrhea), cardiovascular (dysrhythmias, collapse, arrest), gastrointestinal (cramping, vomiting, diarrhea), genitourinary (urgency, cramping), and eye (pruritus, tearing, redness). A biphasic mediator release can occur in up to 20% of cases causing recurrence of symptoms 4 to 8 hours after the initial exposure. Patients on β-blockers are susceptible to an exaggerated allergic response and may be refractory to first line treatment.

Anaphylaxis is a clinical diagnosis. History may confirm exposure to a possible allergen, such as a new drug, food, or sting. There is no specific test to verify the diagnosis in real time; anaphylaxis should be considered in any rapidly progressing multi-system illness. Workup should be directed at ruling out other diagnoses while stabilizing the patient. The differential depends on the organ systems involved and may include myocardial ischemia, gastroenteritis, asthma, carcinoid, epiglottitis, hereditary angioedema, and vasovagal reactions.

Resuscitation must begin with airway, breathing, and circulation. Patients with confirmed or suspected anaphylaxis should be placed on a cardiac monitor with pulse oximetry, and intravenous access should be obtained.

1. Administer oxygen as indicated by oximetry. Angioedema or respiratory distress should prompt early consideration for intubation. Preparations should be made for “rescue” transtracheal jet insufflation or cricothyroidotomy.

2. Limit further exposure. This may be as simple as stopping an intravenous drug or removing a stinger. First aid measures, ice, and elevation may be helpful for local symptoms.

3. First line therapy for anaphylaxis is epinephrine. In patients without cardiovascular collapse, administer 0.3 to 0.5 milligram (0.3 to 0.5 mL of 1:1000; pediatric dose, 0.01 milligram/kilogram to a maximum of 0.5 milligram) intramuscularly in the thigh. The dose may be repeated every 5 min as needed. Patients who are refractory to IM dosing or in significant shock should receive intravenous epinephrine. A bolus of 100 micrograms of 1:100 000 dilution (place 0.1 mL of 1:1000 in 10 mL normal saline) can be given over 5 to 10 min followed by an infusion of 1 to 4 micrograms/min, with close observation for chest pain or arrhythmias.

4. Hypotensive patients require aggressive fluid resuscitation with normal saline 1 to 2 L (pediatric dose, 10 to 20 mL/kilogram).

5. Steroids should be used in all cases of anaphylaxis to control persistent or delayed reactions. Severe cases can be treated with methylprednisolone 125 milligrams IV (pediatric dose, 2 milligrams/kilogram). Mild allergic reactions can be treated with oral prednisone 60 milligrams (pediatric dose, 2 milligrams/kilogram).

6. Every patient with severe allergic symptoms requires antihistamines. Diphenhydramine can be given 50 milligrams IV (pediatric dose, 1 milligram/kilogram). In addition, an H2 blocker such as ranitidine 50 milligrams IV (pediatric dose, 0.5 milligram/kilogram) may be helpful.

7. Bronchospasm can be treated with nebulized β-agonists such as albuterol 2.5 milligrams. If refractory, consider an inhaled anticholinergic, ipratropium bromide 250 micrograms, and intravenous magnesium 2 grams (25 to 50 milligrams/kilogram in children) over 20 to 30 min.

8. For patients on β-blockers with hypotension refractory to epinephrine and fluids, use glucagon 1 milligram IV every 5 min. An infusion of 5 to 15 micrograms/min should be started once blood pressure improves.

9. Angiotensin-converting enzyme inhibitors are a common trigger for nonallergic angioedema. Airway compromise can develop rapidly. Treatment is supportive. Epinephrine, steroids, and antihistamines are often given although benefit has not been proven.

10. Patients with hereditary angioedema do not respond to treatment for anaphylaxis and should be treated with C1 esterase inhibitor replacement. Treatment with fresh frozen plasma has been reported as an alternative when C1 esterase inhibitor replacement is not available.

11. Unstable or refractory patients merit admission to the intensive care unit. Patients with moderate to severe symptoms should be admitted for observation. Patient with mild allergic reactions should be observed in the ED and may be sent home if symptoms are stable or improving. Stable patients who received epinephrine are generally felt to be safe for discharge after 4 hours without symptoms. Consider observing patients with a history of severe reactions and patients on β-blockers for a longer period.

12. Discharge patients on an antihistamine and a short course of prednisone. Counsel all patients about the need to return to the ED in the event of late recurrence of symptoms and about avoiding future exposures to the allergen, if known. All patients who have experienced severe allergic reactions should have and know how to use an epinephrine autoinjector. Consider Medic-Alert bracelets and referral to an allergist in these patients.