Anaphylaxis

GENERAL PRINCIPLES

Definition

Anaphylaxis is a rapidly developing, life-threatening systemic reaction mediated by the release of mast cell and basophil-derived mediators into the circulation.

Classification

• Immunologic anaphylaxis: IgE mediated (type 1 hypersensitivity) or IgG mediated (rare)

• Nonimmunologic anaphylaxis. Previously known as pseudoallergic or anaphylactoid reactions

Epidemiology

Incidence of anaphylaxis is approximately 50-2000 episodes per 100,000 person-years. Fatality is estimated at 0.7%-2% per case of anaphylaxis. In the US, the lifetime prevalence of anaphylaxis is reported to be 1.6%.⁹

Etiology

Immunologic causes

• Foods, especially peanuts, tree nuts, shellfish, finned fish, milk, and eggs

• Insect stings (bees, wasps, and fire ants)

• Medications

• Latex rubber

• Blood products

Nonimmunologic causes

• Radiocontrast media

• Medications (i.e., NSAIDs, opiates, vancomycin, muscle relaxants, rarely ACE inhibitors, and sulfating agents)

• Hemodialysis

• Physical factors (cold temperature or exercise)

• Idiopathic

Pathophysiology

IMMUNOLOGIC

• Anaphylaxis is due to sensitization to an antigen and formation of specific IgE to that antigen. On reexposure, the IgE on mast cells and basophils binds the antigen and cross-links the IgE receptor, which causes activation of the cells with subsequent systemic release of preformed mediators, such as histamine.

• The release of mediators ultimately causes capillary leakage, cellular edema, and smooth muscle contractions resulting in the constellation of physical symptoms.

NONIMMUNOLOGIC

Non-IgE-mediated anaphylaxis is also mediated by direct degranulation of mast cells and basophils in the absence of immunoglobulins.

Risk Factors

• Persistent asthma: increased risk of fatal anaphylaxis if asthma is uncontrolled.

• Cardiovascular disease: increased risk for death in older age.

• Elevated baseline tryptase indicates possible mast cell disorder. Individuals with mastocytosis, a disease characterized by a proliferation of mast cells, are at higher risk for severe anaphylaxis from both IgE- and non-IgE-mediated causes.

• Previous sensitization and formation of antigen-specific IgE with history of anaphylaxis.

• Concomitant use drugs: beta-adrenergic blockers, ACE inhibitors, NSAIDs, alcohol, etc.

• Cofactors such as exercise, fever, acute infection, premenstrual status, and emotional.

• Sensitivity to seafood or iodine does not predispose to radiocontrast media reactions.

Prevention

• For all types of anaphylaxis, recognition of potential triggers and avoidance are the best prevention.

• Self-injectable epinephrine and patient education for all patients with a history of anaphylaxis.

• Radiocontrast sensitivity reactions:

๎ Premedication before procedure include giving prednisone 50 mg PO given 13, 7, and 1 hour before procedure and diphenhydramine 50 mg PO given 1 hour before procedure.

• Premedication is not 100% effective, and appropriate precautions for handling a reaction should be taken.

• Red man syndrome from vancomycin: symptoms can usually be prevented by slowing the rate of infusion and premedicating with diphenhydramine (50 mg PO) 30 minutes before start of the infusion as this is a non-IgE-mediated drug reaction.

DIAGNOSIS

Diagnosis is based primarily on history and physical examination and the documentation of the presence of a specific IgE to the suspected allergen (if the trigger is IgE mediated). Confirmation of anaphylaxis can, in some cases, be provided by the laboratory finding of an elevated serum tryptase level. However, the absence of an elevated tryptase level does not exclude anaphylaxis, particularly if food is the suspected cause.

Clinical Presentation

• The clinical manifestations of allergic and nonimmunologic anaphylaxis are the same.

• Manifestations include pruritus, flushing, urticaria, angioedema, respiratory distress (due to laryngeal edema, Iaryngospasm, or bronchospasm), hypotension, uterine cramping, abdominal cramping, emesis, and diarrhea.

• Most serious reactions occur within minutes after exposure to the antigen, but in some circumstances, the reaction may be delayed for hours. An example is the galactose-α-1,3-galactose allergy that is thought to be triggered by tick bites and is a cause of delayed anaphylaxis (3-6 hours) to red meats including beef, pork, and lamb.

• Some patients experience a biphasic reaction characterized by a recurrence of symptoms after resolution of initial anaphylactic episode. Time range is varied and typically occurs 1-8 hours.

• A few patients have a protracted course that requires several hours to days of continuous supportive treatment.

HISTORY

A thorough history is taken to help identify the potential trigger, such as new foods, medications, or other commonly known allergens. Also documenting the time of onset of symptoms—that is, minutes to hours or days after a suspected exposure—can help to classify the type of anaphylaxis.

PHYSICAL EXAMINATION

• Pay special attention to vital signs: Blood pressure, respiratory rate, and oxygen saturation.

• Airway and pulmonary: Assess for any evidence of laryngeal edema or angioedema. Auscultate lung fields to listen for evidence of wheezing. Continue to assess for need to protect the airway.

• Perform a focused cardiovascular examination.

• Skin: Urticaria or erythema.

Diagnostic Criteria

See Table 11-2 for diagnostic criteria for anaphylaxis.

TABLE 11-2

ANAPHYLAXIS

Anaphylaxis is likely when one of the following three criteria occurs:

1. Acute skin and/or mucosal symptoms (e.g., hives, pruritus, flushing, lip/tongue/uvula swelling) and one of the following:

a. Respiratory symptoms (e.g., wheezing, stridor, shortness of breath, hypoxia)

b. Hypotension or associated end-organ dysfunction (e.g., hypotonia, syncope, incontinence)

2.

a. Skin/mucosal tissue involvement

b. Respiratory symptoms

c. Hypotension or end-organ dysfunction

d. Persistent gastrointestinal symptoms (e.g., emesis, abdominal pain)

3. Decreased blood pressure after exposure to known allergen for the patient:

a. Adults: Systolic blood pressure 30% decrease in systolic blood pressure

b. Infants and children: Hypotension for age or >30% decrease in systolic blood pressure

Modified from Sampson HA, Munoz-Furlong A, Campbell RL, et al. 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. J Allergy Clin Immunol. 2006;117(2):391-397. Copyright ฉ 2006 American Academy of Allergy, Asthma and Immunology. With permission.

Differential Diagnosis

• Anaphylaxis due to preformed IgE and re-exposure: Medications, insect sting, and foods are the most common causes of anaphylaxis.

• Exercise-induced anaphylaxis: anaphylaxis occurs exclusively in association with physical exertion and other cofactors. Triggers include food (wheat, celery, nuts, seafood) and NSAIDs. Treatment would be to avoid exercise immediately after eating causative foods.

• Causes of non-IgE-mediated anaphylaxis

๎ Radiocontrast sensitivity reactions are thought to be from direct degranulation of mast cells in susceptible patients because of osmotic shifts.

๎ Red man's syndrome from vancomycin consists of pruritus and flushing of the face and neck.

๎ Mastocytosis.

๎ Ingestant-related reactions can mimic anaphylaxis. This is usually due to sulfites or the presence of a histamine-like substance in spoiled fish (scombroidosis).

๎ Flushing syndromes include flushing due to red man syndrome, carcinoid, vasointestinal peptide (and other vasoactive intestinal peptide-secreting tumors), postmenopausal symptoms, rosacea, use of niacin, and alcohol use.

• Other forms of shock such as hypoglycemic, cardiogenic, septic, and hemorrhagic.

• Vasovagal syncope can be distinguished from anaphylaxis by the presence of bradycardia; however, bradycardia can occur in anaphylaxis because of the Bezold-Jarisch reflex.

• Respiratory diseases such as acute laryngotracheitis and foreign body obstruction in trachea.

• Miscellaneous syndromes such as hereditary angioedema (HAE; C1 esterase inhibitor [C1 INH] deficiency syndrome), pheochromocytoma, neurologic (seizure, stroke), and capillary leak syndrome.

• Neuropsychiatric causes such as panic attacks or vocal cord dysfunction.

• Idiopathic.

Diagnostic Testing

• Epicutaneous skin testing and serum-specific IgE testing when available to identify trigger allergens.

• Serum tryptase peaks at 1 hour after symptoms begin and may be present for up to 4 hours.

TREATMENT

• Early recognition of signs and symptoms of anaphylaxis is a critical first step in treatment.

• Epinephrine is the medication of choice for treatment of anaphylaxis.

• Maintain recumbent position while assessing and starting therapy.

• Airway management is a priority. Supplemental 100% oxygen therapy should be administered. Endotracheal intubation may be necessary. If laryngeal edema is not rapidly responsive to epinephrine, cricothyroidotomy or tracheotomy may be required.

• Volume expansion with IV fluids may be necessary.

Medications

Epinephrine should be administered immediately. There are no absolute contraindications for treatment with epinephrine in anaphylaxis.

• AdUlt: 0.3-0.5 mg (0.3-0.5 mL of a 1:1000 solution) IM in the lateral thigh, repeated at 10- to 15ญminute intervals if necessary.

• Child: 1:1000 dilution at 0.01 mg/kg or 0.1-0.3 mL administered IM in the lateral thigh, repeated at 10- to 15-minute intervals if necessary.

• 0.5 mL of 1:1000 solution sublingually in cases of major airway compromise or hypotension.

• 3-5 mL of 1:10,000 solution via central line.

• 3-5 mL of 1:10,000 solution diluted with 10 mL of normal saline via endotracheal tube.

• For protracted symptoms that require multiple doses of epinephrine, an IV epinephrine drip may be useful; the infusion is titrated to maintain adequate BP.

Glucagon could reverse refractory bronchospasm and hypotension in patients who are taking β- adrenergic antagonists. Recommended dosage is 1-5 mg intravenously bolus slowly over 5 minutes followed by an infusion at 5-15 μg∕min titrated to clinical response. Monitor for side effects such as nausea and vomiting.

Inhaled β-adrenergic agonists should be used to treat resistant bronchospasm.

Glucocorticoids have no significant immediate effect and may not prevent biphasic reactions. Antihistamines relieve skin symptoms but have no immediate effect on the reaction. They may shorten the duration of the reaction.

• Adult: Diphenhydramine 25-50 mg IM or IV, cetirizine 10 mg oral or IV

• Child: Diphenhydramine 12.5-25.0 mg IM or IV, cetirizine 5-10 mg oral or IV

Referral

Referrals to an allergist for further evaluation should be offered to all patients with a history of anaphylaxis. More importantly, patients with Hymenoptera sensitivity should be evaluated to determine eligibility for venom immunotherapy.