Introduction

Essentials of Diagnosis

• Anaphylaxis is a systemic reaction with cutaneous symptoms, associated with dyspnea, visceral edema, and hypotension.
• Urticaria is characterized by large, irregularly shaped, pruritic, erythematous wheals.
• Angioedema is painless, deep, subcutaneous swelling, often involving periorbital, circumoral, and facial regions.
• These disorders may be diagnosed clinically, especially in the context of allergen exposure; detection of specific IgE or elevated serum tryptase can confirm the diagnosis.

General Considerations
Certain allergens -  especially drugs, insect venoms, and foods -  may induce an IgE antibody response, causing a generalized release of mediators from mast cells and resulting in systemic anaphylaxis. This potentially fatal condition affects both nonatopic and atopic persons. Isolated urticaria and angioedema are more common cutaneous forms of anaphylaxis with a better prognosis.

 

Food allergies cause an estimated 150 fatalities per year in the United States, most cases being due to ingestion of peanuts, tree nuts, shellfish, and fish. Common childhood food allergies such as milk, soy, wheat, and egg are often outgrown over time if strict avoidance is practiced. ß-Lactam antibiotics may be involved in 400-800 fatalities per year, and stinging insect venom causes about 50 fatalities per year. Chronic relapsing urticaria, angioedema, and, less commonly, anaphylaxis, however, are not always due to IgE-mediated hypersensitivity. In a minority of cases -  perhaps 10% or less -  underlying systemic disorders such as systemic mastocytosis or subclinical infection or inflammatory disorders may be manifested by episodic urticaria or angioedema. Idiopathic causes may also be responsible for chronic or relapsing symptoms, suggesting that some cases may be associated with autoimmune processes including the production of histamine-liberating autoantibodies directed against Fce mast cell membrane receptors. Twenty percent of the population will experience urticaria or angioedema during their lifetime, and the estimated prevalence of idiopathic anaphylaxis is 34,000 patients in the United States.

Clinical Findings

A. Symptoms and Signs
The manifestations are (1) hypotension or shock from widespread vasodilation, (2) respiratory distress from bronchospasm or laryngeal edema, (3) gastrointestinal and uterine muscle contraction, and (4) urticaria and angioedema.

B. Laboratory Findings
In vivo allergy skin testing and in vitro RAST testing can detect allergen-specific IgE for a variety of foods, hymenoptera (bee, wasp, hornet, fire ant) venom, latex, and some medicines. Skin testing for food allergy is appropriate only if the patient has symptoms consistent with IgE-mediated allergy (eg, urticaria, angioedema, or anaphylaxis) within 2 hours after eating the suspect food.

Determination of serum tryptase can be used to identify recent anaphylactic reactions or other reactions due to systemic mast cell activation. Tryptase is a mast cell-derived neutral protease with a half-life of 60-90 minutes. Elevated tryptase levels have been associated with anaphylaxis, systemic mastocytosis, and non-IgE-mediated diseases characterized by mast cell degranulation (“anaphylactoid reactions”). Histamine is released during these disorders but has a very short serum half-life, making detection difficult even during symptomatic periods.

If IgE-mediated hypersensitivity is not found and symptoms become relapsing or chronic (over 6 weeks in duration), a screening battery of laboratory tests may be done after a thorough history and physical examination. Appropriate diagnostic testing should follow any positive findings on examination or review of systems.

Treatment
A. Treatment of Anaphylaxis
At the first suspicion of anaphylaxis, airway, breathing, and circulation are assessed. If systemic anaphylaxis is suspected, aqueous epinephrine 1:1000 in a dose of 0.2-0.5 mL (0.2-0.5 mg) is injected intramuscularly. Repeated injections can be given every 5-15 minutes as necessary. Injection in the anterolateral thigh may lead to more predictable and rapid absorption compared with sites in the arm. Epinephrine can stabilize hemodynamics, cause bronchodilation, and prevent further mast cell degranulation. Rapid intravenous infusion of large volumes of fluids (saline, lactated Ringer’s injection, plasma, colloid solutions, or plasma expanders) is essential to replace loss of intravascular plasma into tissues in patients with hypotension caused by marked vasodilation. Other vasopressor drugs (high-dose dopamine, norepinephrine, phenylephrine) may be necessary if the patient remains hypotensive.

Airway obstruction is caused by edema of the larynx and hypopharynx or by bronchospasm. The former is treated by maintenance of an airway with Endotracheal intubation or tracheostomy. Bronchospasm responds to subcutaneous epinephrine or terbutaline. Inhalation of selective ß₂-adrenergic agonists such as albuterol or terbutaline and intravenous administration of aminophylline are effective for bronchospasm.

Antihistamines (H₁- and H₂-receptor antagonists such as diphenhydramine and ranitidine) may be given orally or intravenously and are useful adjuvant therapies for alleviating the cutaneous manifestations of urticaria or angioedema and pruritus and for the gastrointestinal and uterine smooth muscle spasms. Corticosteroids will not reverse respiratory obstruction or shock but may reduce prolonged reactions or relapses. Long-term combined oral antihistamine and prednisone therapy reduces the number and severity of attacks in patients with frequent life-threatening episodes of idiopathic anaphylaxis. Medical therapy does not reliably prevent true IgE-mediated hypersensitivity reactions.

There may be a clinical late-phase response in anaphylaxis, causing a recrudescence of symptoms hours (most commonly 6-12 hours) after exposure to the allergen. Since this may occur after subsidence of the immediate-phase response, all patients with anaphylaxis should be monitored for up to 24 hours.

Anaphylaxis in a patient being treated with ß-adrenergic blocker drugs is a special problem because of refractoriness to epinephrine and selective ß-adrenergic agonists. Higher doses of adrenergic drugs are required for the desired effect; glucagon in patients taking ß-blockers may be beneficial. Patients being treated with angiotensin-converting enzyme (ACE) inhibitors may suffer from more severe hypotension due to blockade of renin-angiotensin-dependent compensatory mechanisms.

B. Treatment of Urticaria and Angioedema
If urticaria or angioedema is found to be secondary to underlying inflammatory or infectious processes, treatment of the primary disorder can lead to remission of cutaneous symptoms.

C. Venom Immunotherapy
Patients with immediate hypersensitivity reactions to stinging insects and documented venom-specific IgE on allergy testing should receive venom immunotherapy for prevention of anaphylaxis. Untreated individuals have a 50-60% risk of anaphylactic response to subsequent stings. Venom immunotherapy is highly protective, affording 98% protection from life-threatening reactions on rechallenge.

Preferences
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Korenblat P et al: A retrospective study of epinephrine administration for anaphylaxis: how many doses are needed? Allergy Asthma Proc 1999;20:383.