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Parents often believe that their child's hives or GI upsets are caused by a sensitivity to a particular food. Confirming their suspicions relies on knowledge of common symptoms of food allergy and a diagnostic process that may or may not include skin prick or blood tests.
|Jump to:||Choose article section... More than one possibility Typical features of food allergy Differential diagnosis TABLE 1 Gastrointestinal syndromes that can be confused with food allergy Making the diagnosis Measuring IgE antibody to food TABLE 2 Blood tests and clinical sensitivity Avoidance is the key to treatment TABLE 3 Terms on food labels that may be confusing Treating acute episodes TABLE 4 Premeasured antianaphylactic agents The big picture The last word|
Parents often believe that their child's hives or GI upsets are caused by a sensitivity to a particular food. Confirming their suspicions relies on knowledge of common symptoms of food allergy and a diagnostic process that may or may not include skin prick or blood tests.
A 7-month-old male who has had atopic dermatitis since he was 1 month of age was breastfed exclusively until his mother began giving him rice cereal when he was 6 months old. This morning, the mother introduces cow milk formula and immediately after drinking it, the infant develops urticaria and begins wheezing and vomiting. The mother rushes into your office with the baby limp in her arms.
This sort of scenario induces fear and anxiety in parents and pediatricians alike. Anaphylaxis, the most extreme manifestation of food allergy, is a medical emergency. Management requires prompt recognition and quick decision making. Once you have successfully treated the acute problem, a search for the underlying cause should begin. Less extreme allergic reactions, such as cutaneous or gastrointestinal symptoms, also call for such an investigation. If you suspect food is the culprit, it is important to pinpoint which one is causing the problem so that you can educate the family about avoiding the food and preventing a recurrence. Understanding the features of immune-mediated food reactions will help you to differentiate food allergy from other adverse food reactions.
An "adverse food reaction" is any untoward reaction to a food, regardless of the mechanism. Adverse food reactions may be further classified as immune-mediated or nonimmune-mediated (also known as intolerance). Immune reactions in which immunoglobulin E (IgE) is produced against a specific food are the best understood type of food allergy (although other mechanisms may exist) and will be the focus of this review. In food intolerance, which takes various forms, the affected individual may have reactions due to toxins or pharmacologic substances contained in the food or due to host-related factors. Caffeine-induced tachycardia, lactose intolerance, and monosodium glutamateassociated flushing (Chinese restaurant syndrome) are examples of food intolerance.
Parents believe that food allergy is common, and one in four adults reports that food allergy affects his or her family. Yet only one third of these "reactions" are confirmed by oral challenge; about half of these confirmed cases are due to allergic mechanisms.1 The incidence of food allergy is age related, with 80% of all food reactions occurring in the first year of life. Several prospective surveys of cow milk allergy have shown a prevalence of 2.5% in the first three years of life.14 The overall prevalence of food allergy is higher in children (5%8%) than in adults (1%2%). The prevalence in certain children may be even greater. A recent study found, for example, that as many as 35% of children with moderate to severe atopic dermatitis also have food allergy.5 Given the role of heredity in developing atopy, food allergy should be considered in those children with a family history of allergy.
Although there are exceptions, most allergenic foods are heat resistant, acid-stable water-soluble glycoproteins. Eggs, cow milk, wheat, soy, and peanut account for 90% of food allergy in American children 5 years of age or younger. Cow milk allergy usually begins in early infancy; onset after 12 months of age is rare.6 Soy protein allergy appears to be less common than previously believed.7 Peanuts, members of the legume family, are not related to tree nuts. Clinical cross-reactivity to legumes is rare.8 In older children and adults, peanuts, tree nuts, fish and shellfish, fruits, and vegetables are common allergens.
Hives and rashes often are associated with food allergy, but gastrointestinal and other symptoms also occur.
Cutaneous reactions. Acute urticaria, angioedema, and pruritus are the most common skin reactions in food allergy. Chronic urticaria and angioedema, defined as lasting six weeks or more, generally are not attributable to food allergy. Though commonly implicated in food allergy, food additives, such as preservatives and dyes, rarely cause chronic urticaria. Fifteen percent or more of cases of atopic dermatitis may be related to food allergy. If the child eats the implicated food frequently, the parent may not associate the food with the rash. After two weeks of dietary restriction, however, the rash will clear in susceptible individuals. Eating the food again induces a pruritic, erythematous rash within 90 minutes or so.9 IgEmediated mechanisms, along with cell-mediated immunity, contribute to the pathogenesis of atopic dermatitis.
Gastrointestinal reactions may occur anywhere from the mouth to the distal large intestine.
Oral allergy syndrome is most common in teenagers and adults who have underlying seasonal allergic rhinitis. In this syndrome, ingestion of certain raw fruits and vegetables induces a form of contact urticaria. Implicated foods such as apples and melons share antigens with inhalant allergens, such as birch tree and ragweed, respectively. Symptoms include pruritus of the lips, oral mucosa, and throat. The patient may also experience mild tightness in the throat, but this condition usually does not progress to significant airway compromise.
More severe reactions affecting the oropharynx include tongue swelling, which may lead to upper airway obstruction.
In gastrointestinal anaphylaxis, symptoms of nausea, abdominal pain, cramps, emesis, or diarrhea occur within two hours of eating. In children with this disorder, chronic ingestion of the culpable food may lead to poor weight gain.
The relationship between foods and allergic eosinophilic gastroenteropathy is not entirely clear; about half of affected children are atopic. Most cases are not found to be due to specific IgE responses to foods.
In allergic eosinophilic esophagitis, symptoms correlate with the extent of eosinophil infiltration. Affected children may vomit, have abdominal pain, find it difficult to swallow (dysphagia), and refuse to eat. In the gastritis and gastroenteritis variants, look for symptoms of postprandial nausea, emesis, diarrhea, early satiety, anorexia, abdominal pain, weight loss, and failure to thrive. Associated findings include peripheral eosinophilia, iron deficiency anemia, and hypoalbuminemia due to protein losses from the gut.
Isolated respiratory symptoms are uncommon in food allergy, though rhinoconjunctivitis, laryngeal edema, and bronchospasm are associated with skin or gastrointestinal symptoms. Studies have shown that the incidence of bronchospasm varies from 6% to 24%, with higher frequency in children with underlying atopic dermatitis.1012 Increased airway hyperresponsiveness has also been associated with food allergy reactions.13 This might lead to greater airway sensitivity to environmental and other airborne allergens in patients with asthma.
Heiner syndrome, commonly known as cow milk protein-induced pulmonary hemosiderosis, is rare. It typically affects young children. Manifestations include cough, wheeze, pulmonary infiltrates, hemosiderosis, gastrointestinal bleeding with iron deficiency anemia, and failure to thrive. Although the exact mechanism is unclear, IgE does not appear to play a role in this disorder. Immunoglobulin G (IgG) production against cow milk has been proposed as a potential mechanism.
Anaphylaxis, depicted in the scenario at the beginning of this article, is the most serious manifestation of food allergy. Several studies have demonstrated that foods are a leading cause of anaphylaxis. The risk for anaphylaxis seems to be related to the allergenic potency of a food as well as the sensitivity of the food-allergic individual. Anaphylaxis occurs when one or more target organs are severely affected by the allergic response.
It is important to note that anaphylaxis is not necessarily accompanied by skin manifestations. Wheezing, cough, and dyspnea develop as a result of bronchospasm; as ventilation decreases, hypoxia ensues. Laryngeal edema may cause cough, hoarseness, throat tightness, drooling, and difficulty speaking or swallowing. Gastrointestinal symptoms include abdominal cramps/pain, vomiting, and diarrhea. Cardiovascular involvement may lead to hypotension and circulatory collapse with ensuing loss of consciousness and death. Some patients report a sense of impending doom; children may become irritable, listless, or unresponsive. These severe reactions occur during or immediately after eating, usually within one to two hours. Frequently, the response is in two phases (biphasic): The patient has a transient immediate reaction, followed by apparent recovery, then severe recurrence of symptoms.
Any food may elicit an anaphylactic reaction, but the most common culprits are peanut, tree nut, fish, and shellfish. It is estimated that 100 Americans die each year because of peanut hypersensitivity. Risk factors for fatal food allergy include a history of asthma, inability to recognize symptoms early, and failure to administer epinephrine promptly.14,15 A rare syndrome of food-dependent exercise-induced anaphylaxis has been reported in teens and adults. Anaphylaxis develops when a patient exercises within four hours of eating a specific food or, rarely, after eating any food. Frequently implicated foods include wheat, celery, and shellfish. As long as the individual refrains from physical activity, the food is well tolerated.
Certain skin eruptions, gastrointestinal syndromes, and respiratory symptoms associated with asthma can be confused with food allergy.
Dermatitis herpetiformis is a pruritic eruption that looks like atopic dermatitis. Eighty-five percent of cases are associated with gluten-sensitive enteropathy.
Many gastrointestinal syndromes have clinical manifestations that overlap with IgEmediated food reactions. Food-induced enterocolitis, for example, generally presents in the first 6 months of life, resulting in sudden onset of emesis, diarrhea (with hemoccult positive watery stools), and dehydration. Acute volume losses may lead to hypotension, making it easy to mistake this syndrome for anaphylactic shock. Adding to the confusion, the foods that usually lead to the enterocolitis include the common food allergens of cow milk, soy, egg, and wheat. Skin tests to these foods are negative, and IgE antibody to implicated foods is not present. Symptoms usually clear within 72 hours of avoiding the food that is responsible, and the long-term prognosis is good since most infants outgrow this problem by 1 year of age. Table 1 outlines non-IgEmediated gastrointestinal syndromes that may be associated with food.
|Celiac disease||Diarrhea Steatorrhea Abdominal distention Flatulence Weight loss Failure to thrive||Total villous atrophy Cellular infiltrate||Gluten (wheat, rye, oat, and, barley)|
|Cow milkassociated anemia in infancy||Occult GI bleed Iron deficiency anemia||Cow milk|
|Dietary protein enteropathy||Diarrhea Steatorrhea Emesis Poor weight gain Failure to thrive Early satiety Malabsorption||Patchy villous atrophy||Cow milk Soy Egg Wheat Rice Chicken Fish|
|Dietary protein proctitis||Blood-streaked stools||Linear erosions Eosinophils Neutrophils||Breast milk Cow milk Soy|
|Food-induced enterocolitis||Emesis Diarrhea Dehydration||Flattened villi Edema Lymphocytes Eosinophils Mast cells||Cow milk Soy Egg Wheat|
Bronchospasm due to asthma may be confused with respiratory symptoms of food allergy.
Foreign body aspiration in a young child may be mistaken for food allergy.
In assessing the child with suspected adverse food reaction, a careful history is imperative. Physical examination and skin testing may also be part of the diagnostic process.
History. Begin by asking about the specific manifestations of the reaction, particularly the time of onset after ingestion. Try to determine if the reported reaction represents intolerance or an immune type of response. IgEmediated food hypersensitivity almost always develops within two hours of eating and frequently occurs within minutes. Delayed reactions are usually caused by factors other than food allergy.
Evaluate the amount of food the child ate and whether he has a reaction each time he eats a particular food. As in other allergic disorders, the amount of allergen required to induce a reaction is small and a clinical response occurs each and every time the food is ingested. In other words, if your patient believes she is allergic to milk and avoids whole milk but eats yogurt or ice cream without difficulty, cow milk proteins are probably not the culprit. Also determine if exercise is part of the picture and whether reactions have required treatment. Obtaining a detailed account of all foods the child has eaten will avoid biases.
Physical examination sometimes is helpful. Evidence of other allergic manifestations, such as allergic rhinitis or asthma and particularly atopic dermatitis, raises suspicion of food allergy. Poor growth or clubbing may indicate the presence of systemic illness. Careful attention to family dynamics and the child's behavior often provides important clues when emotional factors contribute to the underlying problem.
Dietary elimination trial. If you suspect allergy after the initial evaluation, how you proceed depends on the situation. When a single food is associated with immediate onset of anaphylaxis, you may conclude food allergy and defer testing. Counsel the child and family about the importance of abstaining completely from the implicated food, and provide a treatment plan in the event an accident should occur in the future. This is a reasonable approach, especially when the suspect food is nonessential and is highly associated with allergy, for example peanut or shrimp. When cow milk, soy, or wheat is thought to be the culprit, additional testing is warranted since these foods are dietary staples and extremely difficult to avoid over the long term.
When symptoms are mild or chronic, it is useful to eliminate the suspect food from the child's diet and carefully monitor what happens. When the symptoms resolve (or fail to resolve after the food is avoided for two weeks), reintroduce the suspected culprit into the child's diet. If symptoms recur, you are on the right track. If symptoms do not return, the food in question is unlikely to be the cause of the problem. When it is not clear which allergen is culpable, perhaps because the child ate many foods within a short period of time, additional investigation is mandatory. Accurate diagnosis is critical since unnecessary dietary restrictions could lead to nutritional and psychological problems.
Two methods are used to measure the presence of IgE antibody to a specific food.
Skin prick tests. Allergists generally perform the skin prick test, an in vivo method. After applying a drop of allergen extract and appropriate controls, the allergist uses a sharp instrument to prick the skin. Fifteen minutes later, the appearance of a wheal and flare at the positive control and allergen sites indicates that IgE antibody to the allergen is present. It is important to remember that skin testing should be used only in conjunction with the clinical history. Do not base the diagnosis solely on skin tests since they have a false-positive rate as high as 50% to 60%. The false-negative rate is much lower than the false-positive rate, however. In fact, the negative predictive value of food skin testing is greater than 95%.1619 Thus, a negative skin test suggests consideration of alternative causes for the reaction. The positive predictive value of skin tests is higher in infants than in adults, while the negative predictive value is lower in infants than in adults.20
Blood tests. An alternative to skin testing for the primary care provider is the in vitro radioallergosorbent test (RAST). This test quantifies the amount of IgE antibody to a given food by incubating serum with a food allergen extract. Consider RAST when the patient has widespread atopic dermatitis or another skin rash that would make interpretation of skin tests difficult. RAST is also appropriate when dermatographism is present; anti-histamines cannot be discontinued; the child has had a severe, life-threatening anaphylactic reaction; or skin test materials to the suspected allergen are not available. For most foods, RAST has a high sensitivity but a low specificity.21 RAST is expensive and does not provide immediate information the way skin tests do. On the other hand, when properly performed and interpreted, RAST provides important supporting clinical information.
Recently, a modified RAST called the CAP System FEIA has been shown to have more predictive value than skin tests in children with atopic dermatitis and suspected peanut, egg, cow milk, or fish allergy.22 If a patient has a result greater than or equal to the 95% positive predictive value, the child will likely have a clinical reaction to that food (Table 2). In these cases, oral provocation may be deferred. Where the test result is less than the 95% negative predictive value, a reaction is unlikely and the patient may reintroduce the food into the diet. When there is a history of a severe reaction but a "negative" test result, it is a good idea to ask the child to eat the food in the office, before eating it at home, to rule out the slim possibility that the food may induce a reaction.
|Specific IgE/L of sera (CAP System FEIA test only)|
|Food||Sensitivity highly likely (95% positive predictive value)*||Sensitivity highly unlikely (95% negative predictive value)*|
If a test falls between the predictive values, an oral challenge is needed to accurately determine the presence or absence of food allergy. Referral to an allergist may be useful at this point. You might also consider allergy consultation when many foods are implicated. An allergist can help to assess the likelihood that a given food is the culprit when the history is unclear and the RAST reveals multiple potential causes. Allergists can also perform structured oral provocation to suspicious foods, which may help to identify the cause as well as avoid unnecessary food restriction. Although the history is important, only 30% to 40% of cases are validated by blinded challenge, which eliminates parental and physician bias. When placebo controlled and doubled blinded, this type of challenge is generally accepted as the gold standard for diagnosing food allergy.2325 The procedure is best performed in a setting that is equipped to treat anaphylaxis.
Once the diagnosis of food allergy is established, education of children and parents is critical. Reactions will recur with repeated food ingestion, and their severity may vary. The only way to prevent future reactions is to refrain from eating the food. Fortunately, most patients are allergic to only one or two foods. The family that prepares food at home can control the diet by making substitutions in recipes. Eating home-prepared meals has its pitfalls, however. Shared or inadequately cleaned cooking utensils and serving pieces may cause cross contamination. The home cook who uses canned, boxed, or frozen foods to prepare a meal may inadvertently serve the culprit food. Carefully reading labels while shopping at the supermarket is laborious and time-consuming but extremely important. Unfortunately, recognizing the presence of potential food allergens is difficult because labels often use unfamiliar words to designate what a food contains. The words lactalbumin, lactoglobulin, whey, and casein indicate the presence of cow milk proteins, for example. And even a careful deciphering of the label may not be enough to reveal "hidden" allergens.26 Often a label mentions "natural flavoring," for example, but fails to note that the flavoring is derived from cow milk. Certain foods may be added to others because of their physical properties. Casein is used in canned tuna to make it chunky, for example. Table 3 lists ingredients in prepared foods whose derivation may not be clear.
|Caramel color||Cow milk|
|Dairy free||Cow milk|
|Natural flavoring||Cow milk, soy|
|Protein||Soy, milk, egg|
Even if the food label indicates that a particular food is present in minute quantities (as evidenced by its inclusion at the end of the ingredient list), trace amounts of a food can lead to a reaction. Relying on kosher foods is also risky, since dairy free as determined by religious law does not ensure that the food does not contain trace amounts of dairy through contamination or in the form of milk-derived products. On other products, dairy free actually means lactose free (not cow milk protein free). Finally, food manufacturers may suddenly change ingredients, so shoppers need to check labels every time they purchase a food.
Bringing home take-out meals or eating out also is risky because restaurants generally do not provide detailed ingredient lists. This is why most food allergy reactions occur away from home. Children and parents should not assume that a food is safe. They need to question restaurants about the content of the foods they order.
Verbal education of patients and parents about these pitfalls is not enough. Parents need written guides and resources beyond the scope of most physicians' offices. I recommend the Food Allergy Network to every family dealing with the diagnosis of food allergy. This organization, which can be reached on the Web at www.foodallergy.org , offers an impressive array of valuable printed and video material. It also can be reached at a toll-free number: 800-929-4040. This organization may be the single most important referral you make to the families of children with food allergies. The patient also should wear a Medic-Alert bracelet so that important health information is always available.
Accidents happen, no matter how well the patient and family are educated about the child's food allergy. Each family with a food-allergic child needs to have a written emergency plan. It should include the medication name, dose, and route; the clinical indications for the medicines to be given; guidelines for dialing 911 or seeking emergency room care; and an emergency phone number for your office. Copies of the emergency plan should also be available to schools and child-care providers. Figure 1 is a sample of such a plan. The Food Allergy Network also has a form for this purpose.
This child is allergic to: _______________________________________.
If accidental ingestion occurs:
1. Give diphenhydramine ___ tsp by mouth every 6 hours for itching, rash or hives.
2. Administer epinephrine as directed immediately for life-threatening symptoms, such as tongue swelling, choking, difficulty breathing, coughing, wheezing, vomiting, feeling faint, or loss of consciousness.
3. If epinephrine is administered, call 911 or go to nearest emergency department. Also seek emergency care if life-threatening symptoms occur.
______________________________ (after hours)
Should a child eat a food to which he or she is allergic and have a reaction, I recommend using antihistamines in the liquid form for prompt onset of action. Generally, diphenhydramine, 12 mg/kg, is given by mouth immediately and every six hours until the dermatologic manifestations recede. I prescribe epinephrine for children who have had life-threatening reactions and for those who have peanut and tree nut allergy or have asthma in addition to a food allergy. To avoid mistakes in dosing and delays in administration, prescribe premeasured doses of epinephrine. The auto-injectable devices are most convenient. They are easy to use and can be successfully administered through clothing. Table 4 lists available preparations.
|Name of device||Type||Contents||Use|
|Epi-Pen, Jr||Auto-injectable||0.15 mg epinephrine (1:1,000)||Children|
|Epi-Pen||Auto-injectable||0.3 mg epinephrine (1:1,000)||Children >25 kg|
|Ana-Guard||1 mL syringe||1 mg/mL epinephrine (1:1,000)||02 yr: 0.050.1 mL 26 yr: 0.15 mL 612 yr: 0.2 mL 12 yr and up: 0.3 mL|
|Ana-Kit||1 mL syringe||1 mg/mL epinephrine (1:1,000)||Same as guidelines for Ana-Guard|
|Chewable tab||2 mg chlorpheniramine maleate||Under 6 yr: 1 tablet 612 yr: 2 tablets 12 yr and up: 4 tablets|
The child prescribed epinephrine should carry an auto-injectable device at all times, and it should be available at school as well. Indications for intramuscular injection of epinephrine include a history of asthma or a life-threatening reaction or onset of life-threatening symptoms. Emphasize the importance of prompt administration after ingestion of a food to which the child is known to be allergic, since delayed use has been shown to increase the risk of dying from food- induced anaphylaxis. Remember to show the family how to administer epinephrine. "Trainer" devices that simulate the auto-injectable system are available from the manufacturer for demonstration. Caregivers need to have clear instructions for managing reactions at home and for seeking urgent medical care.
Once epinephrine is administered, the child should be taken to the nearest emergency facility for observation and additional treatment, since epinephrine is rapidly metabolized and additional doses may be required. Health-care personnel must quickly assess the severity and extent of the problem, while ensuring airway patency and adequate cardiovascular functioning. Subcutaneous epinephrine may be given at a concentration of (1:1000), 0.01 mg/kg every 15 to 20 minutes to a maximum dose of 0.30.5 mg. Because as many as one third of cases of anaphylaxis are biphasic,27 an observation period of at least four hours in the emergency department or hospital before discharge is advisable. In severe cases, corticosteroids, such as prednisone 12 mg/kg orally or methylprednisolone sodium succinate 12 mg/kg intravenously, should be used to prevent delayed symptoms. Unfortunately, ß-adrenergic agonists, such as albuterol, are often ineffective in relieving bronchospasm caused by anaphylaxis. Epinephrine and oxygen are the preferred initial treatment for respiratory reactions.
Fortunately, the prognosis is good for most children with food allergy. About 30% of them "outgrow" their food allergy after one year of avoiding the implicated food. The food to which the child is allergic but not the severity of the first reaction correlates with persistent sensitivity. In 85% to 90% of children with cow milk allergy, sensitivity remits after three years of avoidance.28 In fact, cow milk, egg, soy, and wheat allergy are usually outgrown. Peanut, tree nut, fish, and shellfish allergy tend to persist into adulthood. Regular reassessment helps to establish whether clinical reactivity has resolved. I usually do this at yearly intervals for the commonly outgrown food allergens. Unfortunately, skin prick tests and RAST may remain positive, even when clinical reactivity is no longer present. Downward trends in these two tests may be a sign of waning reactivity, however.
Oral challenges are the best way to determine whether a child has lost his sensitivity. In spite of the potential risks, this procedure may be performed safely in an allergist's office. I believe the benefits of possible dietary reintroduction generally outweigh the risks of the oral challenge. Life-long dietary restriction is unnecessary for most children suffering from food allergy.
Determination of food allergy in a child with cutaneous or other allergic signs or symptoms calls for a careful history, physical examination, dietary elimination trial, and, sometimes, testing. Once a food allergy has been established, strict avoidance of the culprit and establishment of an emergency treatment plan are essential.
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