About 8 percent of children, or nearly 6 million in the U.S., have a food allergy, a much higher rate than previously estimated, a new study suggests. Not only is this estimate higher than some previous research has reported, allergic reactions are often severe and that many kids have more than one allergy. Of the children with confirmed (or probable) food allergies, about 39 percent had had severe reactions in the past, and 30 percent had more than one allergy, the study found.
In the current study, researchers at the Northwestern University Feinberg School of Medicine surveyed parents of more than 38,000 children about whether their child had been diagnosed with a food allergy and had one or more of a number of symptoms, including anaphylaxis; swelling of the lips, eyes or face and skin rashes or hives.
The study pinned down peanuts (25 percent of food-allergic children), milk (21 percent) and shellfish (17 percent) as the top three allergens. Severe reactions were most common among children with tree nut (more than 50 percent) and fin fish (more than 40 percent) allergies. The reactions were more likely among 14- to 17-year- olds compared with 0- to 2-year-olds, and more likely in children with multiple food allergies, the study found.
FOOD ALLERGY IN CHILDREN
With food allergies on the rise, primary care pediatricians increasingly are faced with the challenges of recognition and care of children with this life-threatening condition. Since diagnostic testing for food allergies can be confusing, families would benefit from a clear explanation from their pediatrician about what to expect and what the results mean for their children. After food allergens are identified, avoidance of these allergens and prompt response to the signs of accidental exposure are the only means to defend against the potentially fatal food-induced anaphylaxis. By providing critical guidance on preventing exposure and the correct use of epinephrine, pediatricians play a key role in helping families effectively protect children with food allergies.
Common food allergies
Food allergies are most often mediated by IgE-induced immunologic mechanisms that cause immediate (ie, within minutes to a few hours) hypersensitivity reactions from urticaria to anaphylaxis. Other types of allergies are also immunologic, but not mediated by IgE. This article will focus specifically on IgE-mediated food allergies.
Food allergies most frequently occur in the first 3 years of life. The most common food allergies in children are milk, egg, and peanut. Adults, on the other hand, are most commonly allergic to shellfish, peanut, and tree nut. This difference reflects the fact that over 75% of children outgrow their milk allergy by 5 years of age and egg allergy by 7 years of age. Recent studies, however, suggest that tolerance to milk and egg develops much later for most children. Only 22% of children at most will develop tolerance to peanuts and less than 10% of patients will outgrow tree nut allergy. Recurrence of peanut allergy is also a risk, found in children who eat peanuts infrequently.
In addition to outgrowing milk and egg allergies, most children will develop tolerance to soy and wheat. Allergies to peanut, tree nut, shellfish, fish and fruits are generally lifelong.
Signs of food allergy
The skin and gastrointestinal tract are most commonly affected by food allergy. Skin manifestations may include pruritus, flushing, rash and urticaria. Acute urticaria may occur after ingestion of a food allergen, whereas chronic urticaria is rarely related to food allergy. Food allergy testing usually is not indicated for chronic urticaria, since most cases are idiopathic.
Up to 35% of children with atopic dermatitis may have food allergy as an underlying trigger. Infants and children with moderate to severe atopic dermatitis, particularly dermatitis refractory to appropriate medical treatment, should be considered for a food allergy evaluation. A history of exacerbation after eating specific foods also might indicate food allergies, but since the reaction is typically delayed, such history is unusual. If food allergy is diagnosed, atopic dermatitis often improves after dietary elimination of that particular food.
Other signs and symptoms of food allergy may include periorbital edema, respiratory symptoms (throat tightness, coughing, wheezing, chest tightness, stridor, etc), gastrointestinal symptoms (oral pruritis, tongue swelling, abdominal cramps, nausea, vomiting, diarrhea), and cardiovascular symptoms (light-headedness, syncope, hypotension). Any or all symptoms could occur, depending on the food allergen, the child’s sensitivity or threshold for reaction, and the quantity consumed.
Food induced anaphylaxis may be life-threatening. Common symptoms of anaphylaxis include dyspnea, urticaria, angioedema, flushing, pruritus, gastrointestinal symptoms, syncope, and hypotension. Cutaneous symptoms are the most common and occur in over 90% of reported cases, but are less common in cases of fatal anaphylaxis. Signs of anaphylaxis typically occur within seconds to minutes after exposure to the allergen, although, rarely, symptoms may occur a few hours later. A late phase reaction may also occur several hours after the initial reaction.
Isolated nasal symptoms related to food allergy are unusual. Multiple nasopharyngeal symptoms may occur with food allergy, including acute rhinitis, but the rhinitis is typically associated with other oropharyngeal symptoms, such as pruritus of the throat and angioedema. Chronic rhinitis, however, is not a manifestation of food allergy.
Diagnostic testing
Food allergy evaluation should begin with a careful medical history. Questions should focus not only on the suspected food, but all foods that were eaten prior to the reaction; the nature of the symptoms; the timing of the reaction with regard to ingestion; and the response to treatment. It is also important to ascertain whether the reaction occurs with each exposure to the suspected food.
If the history suggests an IgE-mediated process, then testing is indicated. Appropriate initial tests for food allergy are serum specific IgE (sIgE) tests, which detect IgE to specific food allergens, or skin prick tests (SPT), which involve introduction of allergen extracts into the skin and measuring the wheal size.
The diagnosis of food allergy is established through clinical history, evidence of sIgE and, depending upon the scenario, an oral food challenge. SPT and sIgE tests provide evidence of sensitization and help determine if/when an oral challenge is appropriate. In situations for which the history is quite clear, such as onset of anaphylaxis within minutes of peanut ingestion with supportive evidence of sIgE to peanut, an oral food challenge is usually not necessary.
Patients may benefit from an oral food challenge if they have borderline SPT or sIgE test results, or if a false positive or false negative result is suspected based on clinical history. Oral food challenges may prevent unjustified food elimination from the diet.
A double-blind, placebo-controlled oral food challenge is the gold standard for diagnosis of food allergy, although open (non-blinded) challenges are generally used in most clinical settings. The patient is given gradually increasing amounts of the suspected food allergen over time. The process usually takes 3-4 hours and requires close physician supervision during the test and for an hour after the test. If the child experiences a severe reaction during the food challenge, a longer observation time is needed.
Testing for specific food allergens must be guided by clinical history, as opposed to testing for all food allergens haphazardly. If a child is already consuming a food without experiencing a clinical reaction, SPT and sIgE testing for that food is not warranted.
Prior to SPT, antihistamines should be discontinued. Generally, the first generation antihistamines are stopped at least 48 hours prior to SPT and second generation antihistamines about 1 week before SPT. In patients with extensive eczema or dermatographia, SPT cannot be performed. The sIgE tests can be used in these cases as the initial test. Antihistamines do not need to be stopped before the sIgE testing.
Interpreting SPT and sIgE test results
In SPT, a positive reaction is defined as a wheal at least 3 mm greater than the negative control. The negative predictive value of SPT is >95%, while the positive predictive value is <50%; therefore, there are many false positive results. The negative results, however, usually reliably identify foods that are safe for the child to eat.
Whether positive SPT results need to be confirmed through sIgE tests or a food challenge depends entirely on the clinical history and the size of the wheal. Positive SPT results are reliable when a large wheal is correlated with the clinical history. For example, a child who within minutes of eating peanuts developed urticaria and angioedema, and who has a positive skin test with a large wheal of 8 mm, does not need a confirmatory sIgE test and definitely does not need a food challenge. In this case, the only reason to get the sIgE test is for a baseline that can be followed every year or so to help predict the likelihood of outgrowing the food allergen. On the other hand, in a child with atopic dermatitis, who has a positive skin test to a food, but did not have a clear history of a reaction, the sIgE test would help to decide whether to perform a food challenge.
For the most part, SPT and sIgE should not be obtained without history of an adverse reaction or moderate to severe atopic dermatitis, as previously stated. If a child tests positive on SPT or sIgE test for a regularly consumed food that does not produce an allergic reaction, it is important to stress to the caregiver that the food continue to be consumed on a regular basis. Because testing indicates that the child is sensitized to the allergen, a prolonged absence of the food from the diet could lead to clinical symptoms upon re-exposure.
Patients with large wheals from SPT or high sIgE values are likely to have allergy to those foods. The cutoff value in the sIgE testing is the concentration of sIgE for a particular food allergen that is 90% predictive of a clinical reaction to the food. For certain foods, cutoff values associated with a high likelihood for a reaction have been published. (See Table 1.) The cutoff values for the wheal diameter and sIgE are different for each food and depend on the age of the child.
Higher levels of sIgE and larger wheal responses to SPT correlate with an increased likelihood of clinical food allergy, but not with the food reaction severity. The severity of a food allergy reaction is unpredictable, and even typically mild reactions to certain foods still pose a risk of anaphylaxis.
Testing for tolerance development
Follow-up testing to evaluate potential development of tolerance is reasonable every 1 to 2 years, depending on the food allergen and the clinical history. Since allergies to peanuts, tree nuts and seafood are less likely to be outgrown, testing for these allergens can be repeated less frequently. Also, if a child reacts to peanuts on accidental exposure 2 years after the last sIgE test to peanuts, for example, there is no need to repeat the test at that time.
Counseling families on preventing exposure
Pediatricians can help families of children with food allergies prevent accidental ingestion by pointing out related foods that also must be avoided. For example, patients with milk allergy also cannot eat yogurt, cheeses, butter, or any product that has milk as an ingredient. The importance of carefully checking ingredient lists of all packaged foods must be stressed, since food antigens may not be apparent in foods such as cookies, cakes or candy. Parents also need to be made aware of non-edible products, such as Play-Doh, toothpaste, or lotions, which may contain allergenic food ingredients and place a child at risk for a dangerous reaction.
The need to avoid foods that might have been cross-contaminated with relevant food allergens during processing, packaging or preparation is another big issue to emphasize to families. Even trace amounts of the food allergen during handling can induce anaphylaxis. Parents of children with allergies to nuts must be particularly vigilant, since many food products that do not contain nuts may have been processed on equipment that was used with nuts.
To prevent cross-contamination at home, separate dishes, utensils, cutting boards, pots and pans should be used if other family members continue to eat foods to which the child is allergic. Similarly, families must be particularly cautious with restaurant food, since even dishes without food allergen ingredients may have been cross-contaminated with those allergens in the kitchen. It is noteworthy that most accidental food reactions occur away from home.
While at school and elsewhere, children should be instructed not to share or trade food with others and to notify adults if they eat something that may contain the food to which they are allergic. Since it can be difficult to determine if foods cooked by someone else are safe for a food-allergic child, it is best to bring foods the child can eat to a birthday party or other social gatherings.
Use of epinephrine
Epinephrine is the primary treatment for anaphylaxis and should be given at the first sign of anaphylaxis. Two epinephrine autoinjectors need to be available at all locations in which a child with food allergies spends an extensive amount of time (eg, home, daycare, school) since a second injection may be required during anaphylaxis before the child reaches the hospital.
Demonstration of the epinephrine auto-injector and written instructions on its use should be provided to the family. Pediatricians also should discuss and provide a written anaphylaxis emergency action plan to the family. In addition, personnel at the child’s daycare or school will need clear instructions on the signs of anaphylaxis, epinephrine use and the emergency action plan. On its website, the Food Allergy and Anaphylaxis Network (FAAN) offers a good emergency action plan that includes instructions on epinephrine use and is available in different languages. The document can be downloaded as a PDF file and distributed freely to patients. See www.foodallergy.org/page/food-allergy-action-plan1. All patients with food allergy should wear a MedicAlert bracelet listing the foods that cause allergic reactions.
After a dose of epinephrine is given, the child should be taken to the closest hospital even if the symptoms have resolved, as they may recur. Parents should be advised that a child with signs of anaphylaxis needs observation in a healthcare setting for at least 4-6 hours.
Epinephrine acts by decreasing vasodilation, edema, and bronchoconstriction. In addition, it suppresses the release of inflammatory mediators from mast cells and basophils. Antihistamines may control urticaria or other symptoms of anaphylaxis, but their use should not be substituted for intramuscular epinephrine. Diphenhydramine and cetirizine can be used in addition to epinephrine, but both medications have a slower onset of action and they do not adequately treat all the underlying mechanisms of anaphylaxis. They should never be used alone for the treatment of anaphylaxis. Corticosteroids are used mainly to control the late phase of anaphylaxis to prevent a rebound in symptoms if the reaction is biphasic. Ranitidine, an H2 antagonist, can have some useful effect, as approximately 15 percent of cutaneous histamine receptors are H2.
Epinephrine should be given intramuscularly in the thigh, as evidence shows more rapid absorption and higher plasma epinephrine levels, compared to subcutaneous injections or intramuscular injections in the upper arm. The new food allergy guidelines that are expected to be released in the fall of 2010 by the National Institute of Allergy and Infectious Diseases (NIAID) recommend the following dosage of 1:1000 epinephrine:
- 0.15 mg for children weighing 10-25 kg (22-55 lbs)
- 0.3 mg for anyone over 25 kg (55 lbs)
Since epinephrine auto-injectors only come in these 2 dosages, the lower dosage is given to children weighing less than 10 kg.
Of note, persons with asthma and food allergies are at higher risk for fatal food-induced anaphylactic reactions. Delayed epinephrine administration is also a risk factor for a fatal outcome. Teenagers with food allergies also are at higher risk for fatal anaphylaxis compared to younger children. Studies have shown that adolescents have poor understanding of when food allergy reactions are severe and when to use epinephrine. In addition, 54% of adolescents admit to intentionally eating potentially unsafe food.
Promising immunotherapy research
There is emerging evidence to suggest that regular ingestion of cooked egg in baked products by egg-allergic children or ingestion of extensively heated milk by milk-allergic children may increase the development of tolerance to these foods. However, without an oral challenge, currently there is no defined method to identify egg/milk-allergic children who would be able to safely consume products with baked egg or heated milk.
Researchers are working on various tests to identify specific protein antigens within allergenic foods (eg, heated milk proteins), which may help predict if a child is going to outgrow the allergen, but these tests are not yet available for clinical use. At this time therefore, strict avoidance of egg and milk allergens is advised until the child has consulted with an allergist.
Other research has been investigating whether tolerance to egg can be induced by a daily dose of egg white solid as oral immunotherapy, with encouraging results. This approach is not recommended for widespread use as studies have yet to determine the right dose, interval, and duration of immunotherapy, as well as the underlying mechanisms that produce tolerance in some patients.
Trials of subcutaneous allergen immunotherapy to many foods had an unacceptably high rate of systemic reactions. However, preliminary studies of oral immunotherapy with peanuts have been very promising. Children who have successfully completed an oral desensitization procedure went from having clinical symptoms with exposure to 1 peanut to tolerating approximately 14 peanuts without suffering an adverse reaction.
Conclusion
Ongoing immunotherapy research offers substantial hope for a viable treatment option for children with food allergies. Until effective treatments are established, however, families of children with food allergies need clear guidance on how to prevent accidental exposure to allergens, recognize symptoms of anaphylaxis, and respond appropriately. Since most children will outgrow their allergies to milk, egg, soy and wheat, follow-up testing will help monitor the development of tolerance and indicate when these foods can be safely reintroduced into the child’s diet. Re-testing for allergens that are less likely to be outgrown can be performed less frequently and in accordance with clinical history.
For Further Reading
[1.] American College of Allergy, Asthma, & Immunology. Food allergy: a practice parameter. Ann Allergy Asthma Immunol 2006;96(3 suppl 2):S1–S68.
[2.] Joint Task Force on Practice Parameters; American Academy of Allergy, Asthma and Immunology; American College of Allergy, Asthma and Immunology; Joint Council of Allergy, Asthma and Immunology. The diagnosis and management of anaphylaxis: an updated practice parameter. J Allergy Clin Immunol 2005;115(3 suppl 2):S483–S523.
[3.] Sicherer SH, Munoz-Furlong, Murphy R, Wood RA, Sampson HA. Symposium: pediatric food allergy. Pediatrics 2003;111(6):1591–1680.
[4.] Lack G. Clinical practice: food allergy. N Engl J Med 2008;359(12):1252–1260.
Author:
Ruchi S. Gupta, MDSpecial interests: Research in the areas of asthma, food allergy and eczema
