Overview and Risk Factors
Anaphylaxis is a rapid, life-threatening, systemic reaction. Although most frequently due to an IgE-mediated immediate-type hypersensitivity reaction, similar symptoms can occur as a result of an antibody-independent anaphylactoid mechanism. In anaphylaxis, activation of mast cells and/or basophils initiates a cascade that affects the respiratory, cardiovascular, integumentary, and gastrointestinal systems. Pathophysiologic processes include inflammation, vasodilation, bronchoconstriction/spasm with airway edema, and mucus secretion.
Common triggers in the hospital include drugs, blood products, and radiocontrast dyes. Outside the hospital, common triggers include venomous insect stings and certain foods, such as eggs, peanuts, dairy products, fish and shellfish, and tree nuts. Allergen-specific immunotherapy is a common cause of anaphylaxis as well.
Age and gender. Allergy and anaphylaxis patterns vary by age and gender, due to stereotypical exposures. For example, adults have more reactions to venomous insects, such as bees, because they are more likely to have been previously exposed, compared with children. Likewise, females are more likely to be sensitized to neuromuscular blockers through a similar chemical in cosmetics.
Atopy. Individuals with a history of allergic diseases are said to be atopic and may have greater risk of severe or fatal reactions to anaphylaxis triggers.
Exposure history. Intravenous exposure tends to cause more severe reactions, because it circumvents epithelial or endothelial exposure barriers. Severity also increases with intermittent dosing (as compared with continuous dosing) or with greater intensity of exposure, as in seasonal or frequent occupational exposures.
History of anaphylaxis. Previous (especially recent) anaphylaxis is a risk factor for recurrence.
Diagnosis and Treatment
Anaphylaxis is a clinical diagnosis. Findings may include:
- Change of mental status.
- Hypovolemic shock.
History of exposure to common triggers should be elicited. A serum antibody test such as enzyme-linked immunosorbent assay (ELISA) or radioallergosorbent test (RAST) drawn concomitantly can help determine the inciting agent, if unknown. Skin testing must be delayed for 6 weeks from the time of exposure.1
When diagnosis is uncertain, testing for levels of plasma histamine, 24-hour urine N-methyl-histamine, and serum/urine tryptase may be helpful.
Cardiopulmonary monitoring and assessment (with intubation if required) and 2 high-volume intravenous access sites are immediately needed. The inciting agent should be removed, if possible. A tourniquet above the site of a venom sting or site of an allergy shot injection may be helpful.
Epinephrine (1:1000) should be administered intramuscularly for mild-to-moderate symptoms, or as soon as the diagnosis of anaphylaxis is considered. It may be self-administered with an EpiPen or similar device and can be repeated at 15-minute intervals en route to an emergency department.
Epinephrine (1:10,000) is used intravenously or through an endotracheal tube for severe symptoms. Glucagon is used intravenously in patients on beta-blockers who do not respond to epinephrine.2
Antihistaminic H1 and H2 blockers should both be used until anaphylaxis resolution. Diphenhydramine and cimetidine are given intravenously.
Oral agents should be considered when more intensive medical care is not immediately accessible.
Solumedrol is administered intravenously.
Inhaled beta-agonists may be used if bronchospasm is present.
If the patient is hypotensive, colloid or crystalloid intravenous fluid should be administered in large volumes. Pressors (dopamine, norepinephrine, phenylephrine, vasopressin) should be used for refractory hypotension.3
Patients with more than mild symptoms should be observed in the emergency department or admitted to the hospital for continued observation, due to risk of recrudescent symptoms after initial improvement.
Allergic Reactions to Foods
Approximately 5% to 10% of young children are allergic to 1 or more foods. The risk for developing allergy may be reduced by late introduction of potentially allergenic foods and by avoidance of those foods by children whose parents have a known allergy to them.4 Although allergic reactions can occur with almost any food, certain items, such as cow's milk, eggs, and nuts, are frequent causes in children, whereas peanuts, tree nuts, fish, and shellfish are the most common in adults.
Most children outgrow their food allergies, leaving 1% to 2% of adults with the condition. Elimination of foods that commonly elicit food allergy and the use of hypoallergenic diets and food-elimination regimens can help to identify or eliminate allergens. Although skin testing and IgE levels are used in diagnosis, the preferred method for food allergy diagnosis is the double-blind, placebo-controlled foods challenge.
Common allergens include milk, egg, peanuts, tree nuts, seeds, wheat, soy, fish, and shellfish. Since these foods are responsible for the vast majority of food allergy reactions,5 avoidance or delayed introduction of them is indicated to prevent allergy. Allergic reactions to these foods have been implicated in food-induced asthma and eosinophilic esophagitis,6 and cow's milk allergy may also contribute to both otitis media and pulmonary hemosiderosis (Heiner's syndrome).7 Some patients react to the presence of the allergens in these foods in amounts as low as 1 mg.8
Fruits and vegetables may occasionally cause food allergy. Many healthful foods, vegetables among them, may cause food allergy. Celery and zucchini can produce allergic reactions even after thorough cooking.9,10 As noted below, patients with pollen allergy often cross-react to many foods.
Allergies may develop as a result of cross-reactivity to foods with similar antigens. Melon frequently elicits allergic reactions, including anaphylaxis, in patients with pollen allergies11 and is highly cross-reactive with allergy to peach.12 Adults with birch pollen allergy (manifesting as rhinitis or asthma) and eczema exhibit late (> 24 hours) allergic reactions after ingestion of foods that cross-react with birch pollen, for example, apple, apricot, carrot, celery, cherry, hazelnut, and pear.13
Persons who are allergic to one fruit are often allergic to others in the same family. Peach, melon, kiwi, apple, and banana accounted for 72% of allergic reactions in a group of adults with rosacea fruit allergy, and cross-reactivity to avocado, apricot, and plum was diagnosed by skin prick testing and IgE determination.14 Patients allergic to latex are often allergic to tropical fruits, such as bananas, kiwi, and avocado. Allergy to citrus fruits, though less commonly reported, causes both oral allergy syndrome (a form of contact dermatitis of the lips, tongue, or other mouth tissues) and systemic allergic reaction.15
Interestingly, a lower frequency of allergic cross-reactivity occurs with the ingestion of plant foods than with the consumption of animal products. The frequency between peanuts and other legumes is <10%, and between wheat and other grains, the frequency is <15%. By comparison, cross-reactivity of mammalian milks (ie, switching from cow's milk to goat's milk) occurs in approximately 90% of cases, and occurs between types of fish with a frequency of 50%.16
Omega-6 fatty acids (found in seed oils and animal products) may increase production of IgE, the main immunoglobulin involved in allergic reactions.17,18 Omega-6 fatty acids also increase production of leukotrienes, which facilitate the allergic response.19,20 These findings suggest that there may be benefit of limiting intake of vegetable oils, margarines, and other sources of omega-6 fatty acids.
Reducing the Likelihood of Allergies
The following steps may help reduce the likelihood that children will develop allergies.
Breast-feeding. Most studies show a protective effect of breast-feeding on food allergy development. In addition, infants at risk for allergies, maternal avoidance of allergenic foods during the first 6 months of breast-feeding reduces the incidence of food allergy.4 If mothers cannot breast-feed, formula should be chosen carefully. Cow's milk allergy is common and often occurs even with partially and extensively hydrolyzed whey formulas, which trigger IgE production. An amino acid-based formula, on the other hand, was found to be nonallergenic.21
Delayed introduction of potentially allergenic foods. In addition to introducing table foods no earlier than 4 to 6 months of age, avoidance of eggs and fish until at least 1 year (if used at all) and of nuts until at least 2 to 3 years is recommended.4
Caution regarding processed foods that may harbor many potential allergens. Patients may be allergic to several foods and food ingredients, and processed food products can be especially problematic. These foods often contain milk, egg, fish, beef, nuts, and seed proteins that are not listed on the product labels, but can cause such reactions as oral allergy syndrome and anaphylaxis. Although processing of certain foods reduces their allergenicity (eg, cutting or heating fruit), most allergens remain stable after processing.22 Eating unprocessed, minimally processed, and homemade foods is likely to decrease this risk. In patients who suspect but cannot confirm food allergy, an elimination diet can be helpful (see below).
Although further studies are needed for confirmation, use of an antigen-avoidance diet for women who are breast-feeding may reduce children's risk of developing atopic eczema in families with a significant family history.23 In infants, older patients with elevated IgE levels, and persons diagnosed with food allergy, elimination diets can help. Diet therapy has been frequently effective in otherwise refractory cases.24 More than 50% of children experience significant improvements in atopic dermatitis during dietary exclusion periods, and roughly one-third outgrow their allergies after 1 to 2 years of avoiding the offending foods.13 To identify foods that trigger atopic dermatitis, an elimination diet can be easily implemented on an outpatient basis, when patients can control their diet for several weeks. The procedure is described below.
Brown, white or puffed rice.
Cooked or dried fruits: cherries, cranberries, pears, prunes, peaches, apricots, papaya, and plums, unless there's a documented allergy to these or to birch pollen.
Cooked green, yellow, and orange vegetables: artichokes, asparagus, broccoli, chard, collards, lettuce, spinach, squash, string beans, sweet potatoes, tapioca, and taro.
Plain or carbonated water.
Condiments: modest amounts of salt, maple syrup, vanilla extract.
When the dermatitis has abated (usually within a week or so), the patient should keep a food diary and add in foods 1 group at a time in generous amounts every 3 to 5 days to observe which cause symptom recurrence. Foods listed above that are most commonly implicated in food allergy should be added last. If the food is associated with allergy symptoms, it should be removed from the diet for 1 to 2 weeks, and reintroduced to see if the same reaction occurs. If no symptoms occur, that food can be kept in the diet. For individuals with a history of anaphylaxis, suspect foods should only be tried under the close supervision of a qualified physician.
Nutrition consultation to instruct patient on avoiding triggers of food allergy and following an elimination diet, and to arrange follow-up.
What to Tell the Family
Food allergy, while common, can usually be diagnosed and treated through allergy testing and avoidance of the offending food(s). Anaphylaxis may occur with consumption of processed foods that contain hidden allergens, and persons who are predisposed to anaphylactic reactions should carry an injectable form of epinephrine, such as an EpiPen or EpiPen Jr. These medications must be stored properly, renewed annually, and kept available for emergencies. Patients and their families should be trained in their use. In families with a history of atopy, the risk for food allergy may be reduced by breast-feeding and late introduction of foods known to cause allergic reactions.
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