Anaphylaxis is an acute, life-threatening, systemic allergic reaction that results from the activation and degranulation of mast cells and/or basophils. Although anaphylaxis is usually due to an immunoglobulin E (IgE)-mediated (allergic antibody) immediate-type hypersensitivity reaction, similar symptoms can occur as a result of an antibody-independent or anaphylactoid-mediated activation. Common triggers include medications, insect stings, and foods such as eggs, peanuts, dairy products, fish and shellfish, and tree nuts. Transfusion of blood products, radiocontrast media, and allergen-specific immunotherapy (allergy injections) also pose a risk of anaphylaxis. Although not common, certain meats can also cause anaphylaxis with symptoms developing several hours after the exposure.[1]

Food allergies affect as much as 4% of the US population.[2] Food proteins may initiate an immune response in sensitized individuals. The spectrum of symptoms due to allergy is broad, affecting the eyes, nose, throat, skin, and gastrointestinal tract. Respiratory symptoms are the most life-threatening and include swelling of the airway (angioedema), which can lead to asphyxiation and death.

Risk Factors

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. These include patients with asthma.

Age and sex. Allergy and anaphylaxis patterns vary by age and sex. Adults have more medication reactions than children do, simply because they typically take more medications than younger people, and adults react more frequently to bees and other venomous insects because they are more likely to have been previously exposed. Likewise, females are more likely to be sensitized to neuromuscular blockers through a similar chemical exposure in cosmetics.

Exposure history. Intravenous exposure tends to cause more severe reactions because it circumvents epithelial or endothelial exposure barriers. Severity also increases with intermittent dosing 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.

Ulcer prophylaxis. Some evidence suggests that patients using H2-receptor blockers and proton pump inhibitors may have increased IgE reactivity to common dietary components with increased risk of anaphylaxis, but further study is needed.[3]

Diagnosis

Anaphylaxis is a clinical diagnosis based on symptoms and a detailed history of the episode. Findings may include:

• Skin/mucosa: Flushing, pruritus, urticaria, angioedema (lips, tongue, periorbital), diaphoresis. Skin and/or mucosal findings are almost always present, and often in conjunction with one of the symptoms below.
• Respiratory compromise: Dyspnea, wheezing/stridor, rhinitis, cough.
• Systemic cardiovascular compromise: Hypotension, tachycardia, dizziness, syncope, changes in mental status, hypovolemic shock.
• Gastrointestinal/urogenital compromise: Nausea, vomiting, abdominal pain, diarrhea, incontinence.

History of exposure to common triggers should be elicited. A serum antibody test, such as enzyme-linked immunosorbent assay or radioallergosorbent test, may be used to determine the IgE response to various allergens.

Skin testing and IgE levels may be used in the diagnosis of food allergies. When diagnosis of anaphylaxis is uncertain, testing for levels of plasma histamine, 24-hour urine N-methylhistamine, and serum/urine tryptase may be helpful but will not indicate the etiology. Tryptase elevation is seen more frequently with anaphylaxis caused by insect stings or medication than from foods.

Treatment

The inciting agent should be avoided, if possible.

Epinephrine (1:1,000) should be administered intramuscularly as soon as anaphylaxis is suspected. It may be self-administered with an EpiPen or similar device. Dosing can be repeated every 15 minutes en route to an emergency department, as nearly 50% of episodes occur in the home. For severe symptoms, epinephrine (1:10,000) is administered intravenously or through an endotracheal tube. Most fatalities occur when epinephrine administration is delayed. Glucagon is used intravenously in patients on beta-blockers who do not respond to epinephrine.[4]

Cardiopulmonary monitoring and assessment (with intubation in cases of marked respiratory distress), supplemental oxygen, and 2 large-bore intravenous access sites are immediately needed.

Antihistaminic H1 blockers should be used in conjunction with epinephrine until resolution of anaphylaxis. Diphenhydramine is given intravenously. H2 blockers (e.g., cimetidine) are no longer used because they have not shown significant benefit compared with placebo.

Oral agents should be considered when more intensive medical care is not immediately accessible. Antihistamines relieve hives and pruritus but will not improve airway obstruction, and they can potentially worsen the hypotension.[5]

Methylprednisolone may be administered intravenously, but it does not relieve the initial symptoms of anaphylaxis due to its delayed onset of action (several hours).

Inhaled beta-agonists (e.g., albuterol) may be used if severe bronchospasm is present; however, they should never be used on their own as they do not relieve upper airway obstruction.

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.

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 recurring symptoms after initial improvement (i.e., biphasic anaphylaxis reaction).

Nutritional Considerations

Allergic Reactions to Foods

Food allergies were identified in 8% of children and 11% of adults in the US.[6],[7] The Centers for Disease Control and Prevention estimated that childhood food allergies increased by 18% between 1997 and 2007.[8],[9] The figure for adults is lower because some people outgrow childhood food allergies.

Guidelines issued by the American Academy of Pediatrics suggest that a delayed introduction of potentially allergenic foods in the first year of life does not seem to be beneficial for allergy prevention.[10] Similar conclusions were drawn from the Learning Early About Peanut Allergy (LEAP) trial, in which 640 high-risk infants between the ages of 4 months and 11 months were randomly assigned either to consume peanut products 3 or more times per week or to completely avoid peanut products for the first 5 years of life. The LEAP investigation found that more than 17% in the peanut avoidance group developed peanut allergy by 5 years compared with roughly 3% in the peanut consumption group.[10]

Common allergens include milk, egg, peanuts, tree nuts, seeds, wheat, soy, fish, and shellfish. These foods are responsible for the vast majority of allergic reactions, including food-induced asthma and eosinophilic esophagitis.[11],[12],[13] Cow’s milk may also contribute to both otitis media and pulmonary hemosiderosis (Heiner syndrome) in young children.[14] Some patients react to the presence of the allergens in these foods in amounts as low as 1 mg.[15] Allergic reactions also appear to differentially affect people by age: Cow’s milk, eggs, soybeans, and peanuts are frequent causes in children, whereas peanuts, tree nuts, fish, and shellfish are the most common ones in adults. These last 4 are most often responsible for food-induced anaphylaxis and are often not outgrown, although up to 20% of children experience resolution of peanut allergy by the time they start elementary school.[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.[16],[17] As noted below, patients with pollen allergy often cross-react to many foods.

Sensitization may develop as a result of cross-reactivity to allergens in both pollen and certain foods, known as pollen food allergy syndrome (PFAS) or oral allergy syndrome. Melon proteins may cross-react with pollen proteins and are highly cross-reactive with proteins contained in peaches.[18],[19] Adults with birch pollen allergy, for example, may develop itching and swelling of the tongue, roof of mouth, or throat after ingestion of foods that cross-react with birch pollen, including apple, apricot, carrot, celery, cherry, hazelnut, and pear.[20]

Persons who are allergic to 1 fruit are often allergic to others in the same family. For instance, peach, melon, kiwi, apple, and banana frequently cross-react with avocado, apricot, and plum and may be diagnosed via skin prick testing, although IgE testing may be negative.[21] 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 PFAS and systemic allergic reaction.[22]

Interestingly, a lower frequency of allergic cross-reactivity occurs with the ingestion of plant foods than with the consumption of animal products. The frequency of cross-reactivity between peanuts and other legumes is < 10%, and between wheat and other grains is < 15%. By comparison, cross-reactivity between mammalian milks (i.e., cow’s milk versus goat’s milk) occurs in approximately 90% of cases and occurs between types of fish with a frequency of 50%.[23] Reports of allergic reactions to meats (beef, pork, and lamb) are also likely to increase, especially in southern states where tick bites are common. The antigen responsible for inducing an IgE-mediated allergic response in this case is galactose-alpha-1,3 galactose, which is found both in red meat and in ticks. Reactions to eating meat in individuals bitten by ticks occur after a prolonged period (4 to 6 hours or longer), although alcohol ingestion and exercise may shorten this time. Affected individuals may need to avoid both meat and dairy products in order to prevent reactions, which range from pruritis to anaphylaxis.[24]

Omega-6 fatty acids (found in seed oils and animal products) may increase production of IgE, the main immunoglobulin involved in allergic reactions.[25],[26] Omega-6 fatty acids may also increase production of leukotrienes, which facilitate the allergic response.[27],[28] These findings suggest that there may be a benefit in limiting intake of vegetable oils, margarines, and other sources of omega-6 fatty acids. Conversely, there is evidence that a higher intake of omega-3 fatty acids is protective against the development of food allergy (see below).

Dietary supplements, spices, and preservatives may cause allergic or anaphylactic reactions. Royal jelly, willow bark, Echinacea, and fruit-containing herbal teas have been known to cause anaphylactic reactions.[29],[30],[31],[32] Rarely, anaphylactic reactions to vitamin supplements have occurred, including reactions to synthetic folic acid, synthetic vitamin B5 (dexpanthenol, the stable alcohol of pantothenic acid), and synthetic forms of thiamine (vitamin B1) and riboflavin (vitamin B2).[33],[34],[35] Individuals with orofacial granulomatosis are particularly sensitive to food preservatives including benzoic acid, cinnamon compounds, chocolate, and artificial flavorings. Following a cinnamon- and benzoate-free diet provides relief in 54-78% of patients.[36]

Reducing the Likelihood of Allergies

The following steps may help reduce the likelihood that children will develop allergies.

Breastfeeding. An American Academy of Pediatrics review concluded that breastfeeding for at least 4 months may prevent or delay the occurrence of atopic dermatitis, cow’s milk allergy, and wheezing in early childhood, when compared with feeding formula made with intact cow’s milk protein.[37] If mothers do not breastfeed, formula should be chosen carefully. Cow’s milk allergy is common and may occur even with partially and extensively hydrolyzed whey formulas, which trigger IgE production. An amino acid-based formula, alternatively, was found by 1 study to be less allergenic.[38] A recent systematic review concluded that there is no good evidence to recommend that pregnant or breastfeeding women should change their diets apart from adopting an overall healthful diet, or take supplements to prevent allergies in infants at high or normal risk.[39] Possible exceptions to this may include probiotic- and omega-3 fatty acid-containing foods and supplements (see below).

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 reactions such as oral allergy syndrome and anaphylaxis. Although processing of certain foods reduces their allergenicity (e.g., cutting or heating fruit), most allergens remain stable after processing.[40] In some cases (e.g., roasting peanuts), processing increases allergenicity.[4] 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).

Supplemental probiotics and omega-3 fatty acids may be helpful. A systematic review and meta-analysis of studies found that supplementing mothers and children with probiotics, both prenatally and postnatally, significantly reduces the risk of developing food sensitization as confirmed by positive skin prick tests and/or elevated IgE to food antigens.[41] These results may be explained by the “hygiene hypothesis,” which postulates that decreased exposure to commensal microbes and infections, wide use of antibiotics, and other elements of a Western lifestyle contribute to reduced gut microbe diversity, correlating with the emergence of allergic diseases.[42] A Cochrane review found a significant reduction in food allergies in infants between birth and 12 months of age whose mothers had taken omega-3 supplements prenatally or during breastfeeding. The study also found a significant reduction in egg sensitization in the same children between the ages of 12 months and 36 months.[43]

Household exposure to a dog or cat during infancy has been shown to protect against childhood allergy and asthma.[44]

Elimination Diets

Parents concerned with symptoms that are refractory to treatment in a child may frequently assume a food allergy is the cause and restrict a child’s diet to a greater extent than necessary. Consequently, kwashiorkor, rickets, vitamin-mineral deficiencies, and comparative reductions in growth have been identified in children on allergy elimination diets when compared with those on unrestricted diets.[45] Children with food protein-induced enterocolitis syndrome may be particularly at risk because they are known to react to foods thought to be nonallergenic, including rice and oats, as well as fruits, vegetables, and meats.[46] Nevertheless, an antigen-avoidance diet for women who are breastfeeding may be used to reduce children’s risk of developing atopic eczema in families with a significant family history.[47] In infants, older patients with elevated IgE levels, and persons diagnosed with food allergy who experienced atopic eczema/dermatitis, excluding certain foods (most often, cow’s milk and eggs) has been shown to reduce symptoms of this skin condition.[48] Diet therapy has frequently been effective (52-80% of patients) in severe or otherwise refractory cases of atopic eczema/dermatitis.[48] More than 50% of children experienced significant improvements in atopic dermatitis during dietary exclusion of cow’s milk and eggs, and roughly one-third outgrew their allergies after 1 to 2 years of avoiding the offending foods, with the exception of nuts and shellfish, which typically continue to elicit reactions.[20] To identify foods that trigger atopic dermatitis, an elimination diet can be implemented on an outpatient basis. The procedure is described below.

Start with a baseline diet made up of only those foods not implicated in food allergy, and eliminate cow’s milk, eggs, tree nuts, peanuts, fish, shellfish, and wheat. Well-tolerated foods include:

Grains: brown, white, and puffed rice, and gluten-free grains such as amaranth, millet, and buckwheat.

Cooked and dried fruits: cherries, cranberries, pears, prunes, peaches, apricots, papaya, and plums, unless there is a documented allergy to these.

Cooked green, yellow, and orange vegetables: artichokes, asparagus, broccoli, chard, collards, lettuce, spinach, squash, string beans, sweet potatoes, tapioca, and taro.

Plain and carbonated water.

Condiments: modest amounts of salt, maple syrup, or 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 3-5 days to observe which foods cause symptom recurrence. Foods listed above that are most implicated in food allergy should be added last. If the food is associated with allergy symptoms, it should be removed from the diet for 1-2 weeks and then reintroduced under the supervision of an allergist to see if the same reaction occurs. If no symptoms occur, that food may be kept in the diet. For individuals with a history of anaphylaxis, suspect foods should be tried only under the close supervision of a qualified physician.

Orders

See Basic Diet Orders chapter.

Nutrition consultation to instruct patient on avoiding triggers of food allergy and following an elimination diet, as well as 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 breastfeeding, limiting unnecessary use of antimicrobial products, and early exposure to foods.

References