Anaphylaxis

By Peter J. Delves, PhD, University College London, London, UK

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Allergic, Autoimmune, and Other Hypersensitivity Disorders

Overview of Allergic and Atopic Disorders
Allergic Rhinitis
Anaphylaxis
Angioedema
Hereditary and Acquired Angioedema
Autoimmune Disorders
Drug Hypersensitivity
Food Allergy
Mastocytosis

Anaphylaxis is an acute, potentially life-threatening, IgE-mediated allergic reaction that

occurs in previously sensitized people when they are reexposed to the sensitizing
antigen. Symptoms can include stridor, dyspnea, wheezing, and hypotension. Diagnosis
is clinical. Treatment is with epinephrine. Bronchospasm and upper airway edema may
require inhaled or injected beta-agonists and sometimes endotracheal intubation.
Persistent hypotension requires IV fluids and sometimes vasopressors.

Etiology
Anaphylaxis is typically triggered by

Drugs (eg, beta-lactam antibiotics, insulin, streptokinase, allergen extracts)

Foods (eg, nuts, eggs, seafood)

Proteins (eg, tetanus antitoxin, blood transfusions)

Animal venoms

Latex

Peanut and latex allergens may be airborne. Occasionally, exercise or cold exposure (eg, in patients with
cryoglobulinemia) can trigger or contribute to an anaphylactic reaction.

History of atopy does not increase risk of anaphylaxis but increases risk of death when anaphylaxis occurs.

Pathophysiology
Interaction of antigen with IgE on basophils and mast cells triggers release of histamine, leukotrienes, and
other mediators that cause diffuse smooth muscle contraction (eg, resulting in bronchoconstriction,
vomiting, or diarrhea) and vasodilation with plasma leakage (eg, resulting in urticaria or angioedema).

Anaphylactoid reactions
These reactions are clinically indistinguishable from anaphylaxis but do not involve IgE and do not require
prior sensitization. They occur via direct stimulation of mast cells or via immune complexes that activate
complement.

The most common triggers of anaphylactoid reactions are

Iodinated radiopaque contrast agents

Aspirin and other NSAIDs

Opioids

Ig

Exercise

Symptoms and Signs

Symptoms of anaphylaxis typically begin within 15 min of exposure and involve the skin, upper or lower
airways, cardiovascular system, or GI tract. One or more areas may be affected, and symptoms do not
necessarily progress from mild (eg, urticaria) to severe (eg, airway obstruction, refractory shock), although
each patient typically manifests the same reaction to subsequent exposure.
Symptoms range from mild to severe and include flushing, pruritus, urticaria, sneezing, rhinorrhea, nausea,
abdominal cramps, diarrhea, a sense of choking or dyspnea, palpitations, and dizziness.

Signs of anaphylaxis include hypotension, tachycardia, urticaria, angioedema, wheezing, stridor, cyanosis,
and syncope. Shock can develop within minutes, and patients may have seizures, become unresponsive,
and die. Cardiovascular collapse can occur without respiratory or other symptoms.

Late-phase reactions may occur 4 to 8 h after the exposure or later. Symptoms and signs are usually less
severe than they were initially and may be limited to urticaria; however, they may be more severe or fatal.

Diagnosis
Clinical evaluation

Sometimes measurement of 24-h urinary levels of N-methylhistamine or serum levels of tryptase

Diagnosis of anaphylaxis is clinical. Anaphylaxis should be suspected if any of the following suddenly
occur without explanation:

Shock

Respiratory symptoms (eg, dyspnea, stridor, wheezing)

Two or more other manifestations of possible anaphylaxis (eg, angioedema, rhinorrhea, GI

symptoms)

Risk of rapid progression to shock leaves no time for testing, although mild equivocal cases can be
confirmed by measuring 24-h urinary levels of N-methylhistamine or serum levels of tryptase.

The cause is usually easily recognized based on history. If health care workers have unexplained
anaphylactic symptoms, latex allergy should be considered.

Pearls & Pitfalls

Consider latex allergy in health care workers with unexplained anaphylactic
symptoms.

Treatment
Epinephrine given immediately

Sometimes intubation

IV fluids and sometimes vasopressors for persistent hypotension

Antihistamines

Inhaled beta-agonists for bronchoconstriction

Epinephrine
Epinephrine is the cornerstone of treatment for anaphylaxis; it may help relieve all symptoms and signs
and should be given immediately.

Epinephrine can be given sc or IM (usual dose is 0.3 to 0.5 mL of a 1:1000 [0.1%] solution in adults or
0.01 mL/kg in children, repeated every 10 to 30 min). Maximal absorption occurs when the drug is given
IM in the lateral thigh.

Patients with cardiovascular collapse or severe airway obstruction may be given epinephrine IV in a single
dose (3 to 5 mL of a 1:10,000 [0.01%] solution over 5 min) or by continuous drip (1 mg in 250 mL 5%
D/W for a concentration of 4 mcg/mL, starting at 1 mcg/min and titrated up to 4 mcg/min [15 to 60
mL/h]). Epinephrine may also be given by sublingual injection (0.5 mL of 1:1000 solution) or through an
endotracheal tube (3 to 5 mL of a 1:10,000 solution diluted to 10 mL with saline). A second injection
of epinephrine sc may be needed.

Glucagon 1-mg bolus (20 to 30 mcg/kg in children) followed by 1-mg/h infusion should be used in patients
taking oral beta-blockers, which attenuate the effect of epinephrine.

Other treatments
Patients who have stridor and wheezing unresponsive to epinephrine should be given O2 and be intubated.
Early intubation is recommended because waiting for a response to epinephrine may allow upper airway
edema to progress sufficiently to prevent endotracheal intubation and require cricothyrotomy.

Hypotension often resolves after epinephrine is given. Persistent hypotension can usually be treated with 1
to 2 L (20 to 40 mL/kg in children) of isotonic IV fluids (eg, 0.9% saline). Hypotension refractory to fluids
and IV epinephrine may require vasopressors (eg, dopamine 5 mcg/kg/min).

Antihistaminesboth H1 blockers (eg, diphenhydramine 50 to 100 mg IV) and H2 blockers

(eg, cimetidine 300 mg IV)should be given q 6 h until symptoms resolve.

Inhaled beta-agonists are useful for managing bronchoconstriction that persists after treatment
with epinephrine; albuterol 5 to 10 mg by continuous nebulization can be given.

Corticosteroids have no proven role but may help prevent a late-phase reaction; methylprednisolone 125
mg IV initially is adequate.

Prevention
Primary prevention is avoidance of known triggers. Desensitization is used for allergen triggers that cannot
reliably be avoided (eg, insect stings).

Patients with past reactions to a radiopaque contrast agent should not be reexposed. When exposure is
absolutely necessary, patients are given 3 doses of prednisone 50 mg po q 6 h, starting 18 h before the
procedure, and diphenhydramine 50 mg po 1 h before the procedure; however, evidence to support the
efficacy of this approach is limited.

Patients with an anaphylactic reaction to insect stings, foods, or other known substances should wear an
alert bracelet and carry a prefilled, self-injecting epinephrine syringe (containing 0.3 mg for adults and
0.15 mg for children) and oral antihistamines for prompt self-treatment after exposure.

Key Points
Common triggers of anaphylaxis include drugs (eg, beta-lactam antibiotics, allergen extracts),
foods (eg, nuts, seafood), proteins (eg, tetanus antitoxin, blood transfusions), animal venoms, and
latex.
 NonIgE-mediated reactions that have anaphylactic-like manifestations (anaphylactoid reactions)
can be caused by iodinated radiopaque dye, aspirin, other NSAIDs, opioids, blood transfusions, Ig,
and exercise.

Consider anaphylaxis if patients have unexplained hypotension, respiratory symptoms, or 2

anaphylactic manifestations (eg, angioedema, rhinorrhea, GI symptoms).

Give epinephrine immediately because anaphylactic symptoms may rapidly progress to airway
occlusion or shock; epinephrine can help relieve all symptoms.

Last full review/revision June 2016 by Peter J. Delves, PhD