Food allergies have become a growing public health concern. At present the standard of care focuses on avoidance of trigger foods, education, and treatment of symptoms following accidental ingestions. This article provides a framework for primary care physicians and allergists for the diagnosis, management, and treatment of pediatric food allergy.
Key points
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There are no proactive treatments currently available for food allergy.
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Severe life-threatening reactions typically only occur following oral ingestion.
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Identifying the potential food trigger is critical, and diagnostic testing along with clinical history is needed for diagnosis, with a food challenge being confirmative.
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Providers should teach recognition and treatment of allergic reactions and provide an emergency action plan.
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Children with food allergies should be seen annually to assess for interval ingestions, provide education, and monitor for tolerance.
Introduction
Food allergy affects approximately 8% of children in the United States. Of those children with food allergies, 38.7% have experienced a severe reaction. At present there are no proactive treatments available for food allergy; consequently, the mainstay of therapy is education and avoidance. Often pediatricians are the first physicians encountered by patients with food allergies; therefore, it is critical that pediatricians are trained in the principles of proper diagnosis, management, and referral. This article reviews the 5 main steps of food allergy management in a primary care clinic: (1) clinical history and physical examination, (2) appropriate use of diagnostic testing, (3) medication, (4) counseling/education for patients and families, and (5) referral to an allergist.
Introduction
Food allergy affects approximately 8% of children in the United States. Of those children with food allergies, 38.7% have experienced a severe reaction. At present there are no proactive treatments available for food allergy; consequently, the mainstay of therapy is education and avoidance. Often pediatricians are the first physicians encountered by patients with food allergies; therefore, it is critical that pediatricians are trained in the principles of proper diagnosis, management, and referral. This article reviews the 5 main steps of food allergy management in a primary care clinic: (1) clinical history and physical examination, (2) appropriate use of diagnostic testing, (3) medication, (4) counseling/education for patients and families, and (5) referral to an allergist.
Clinical history
A pertinent clinical history is the single most important tool a physician should use in the diagnosis of pediatric food allergy. Many patients may report symptoms related to food ingestion, but key historical elements can distinguish food allergies from other food-related disorders. All allergic disorders have their roots in inappropriate immune responses, from immunoglobulin E (IgE)-mediated immediate hypersensitivity (eg, anaphylaxis) to non–IgE-mediated conditions.
Differential Diagnosis
The differential diagnosis of food allergy is broad, and encompasses immune-mediated and non–immune-mediated processes. Table 1 details the differential diagnosis of adverse reactions to foods.
| Mechanism | Disorder | Example |
|---|---|---|
| Immune mediated | Celiac disease | Wheat ingestion results in abdominal pain, diarrhea, vomiting, and weight loss |
| Eosinophilic gastrointestinal disorders | Ingestion of dairy products causes eosinophilic esophagitis manifesting as failure to thrive, vomiting, dysphagia, or food impaction | |
| Food protein-induced enterocolitis syndromes | Severe vomiting and hypotension hours after rice ingestion | |
| IgE-mediated food allergy | Severe anaphylaxis caused by peanut ingestion | |
| Milk protein allergy | Milk ingestion leads to bloody stools, diarrhea, and failure to thrive during the first few months of life | |
| Pollen-food allergy syndrome | Sensitization to birch pollens results in oropharyngeal symptom following consumption of raw apple or carrots | |
| Non–immune mediated | Auriculotemporal (Frey) syndrome | Gustatory flushing caused by foods |
| Chemical effects | Gustatory rhinitis caused by hot/spicy foods | |
| Food intolerance/aversion | Nonspecific symptoms resulting in unwillingness to ingest a particular food | |
| Metabolic disorders | Lactose intolerance characterized by abdominal pain, distension, and diarrhea following milk ingestion | |
| Pharmacologic reactions | Adverse effects related to caffeine, tryptamine, or alcohol consumption. | |
| Toxic reactions | Scromboid fish toxin, food poisoning |
Allergy Versus Intolerance
Food allergies are often mistakenly defined as any adverse reaction owing to ingestion of specific foods or types of food. A true food allergy is an immunologic reaction leading to effector cell (ie, mast cell, basophil, T cell) activation, which results in a stereotypic clinical presentation (see later discussion). Many patients and some clinicians may attribute disorders such as celiac disease or irritable bowel syndrome to food allergies. Although some of these disorders certainly have immunologic underpinnings, they can largely be distinguished from hypersensitivity reactions based on key findings in the clinical history such as timing, reproducibility, and symptom complex. For example, a teenage patient who newly develops abdominal pain and diarrhea alone 6 hours after drinking a glass of milk is more likely to have lactose intolerance than an IgE-mediated milk allergy. Adverse reactions such as these should be labeled as intolerances and managed appropriately. Described here are salient clinical features that will assist in distinguishing IgE-mediated food allergies from other adverse reactions to foods.
Suspected Triggers
Although children can be allergic to any food, the 8 most common pediatric food allergens are peanut, cow’s milk, shellfish, tree nuts, egg, fin fish, wheat, and soy. Often families may be unsure of the exact food that precipitates a reaction. Common food allergens are usually explicitly stated on food labels. However, in cases where a trigger is not obvious, clinicians must assess the potential for cross-contamination, which commonly occurs in bakeries, buffets, ethnic restaurants, and ice cream parlors, among other locations.
The pathogenesis of IgE-mediated food allergies requires antigen exposure for sensitization to occur. Of note, most childhood food allergies are detected when the child is first introduced to the food. Recent evidence suggests that cutaneous exposure in the context of barrier disruption (ie, atopic dermatitis), presumably early in life, may lead to food sensitization. This aspect has important implications for food allergy prevention, as recent literature suggests that early oral exposures may be important for inducing tolerance. In a landmark study, Du Toit and colleagues demonstrated that children 4 to 11 months of age randomized to early oral exposure to peanut versus avoidance had an 86% reduction in the incidence of peanut allergy by 5 years of age. Previous guidelines to avoid potentially allergenic foods during the first few years of life are no longer recommended, and may actually lead to food sensitization.
Type of Reaction
IgE-mediated reactions are distinguished by rapid onset (usually within 2 hours of ingestion) and typically resolve within 24 hours. Characteristic symptoms may include any of the following alone or in combination: hives, swelling/angioedema, vomiting, respiratory compromise, and anaphylaxis. Less common symptoms may include eczematous rash (late onset), rhinorrhea, diarrhea, or abdominal pain. Clinicians should note which medications (antihistamines, epinephrine) were administered and the type of medical care that was given. Additional factors such as alcohol ingestion, exercise, concurrent fever, and use of nonsteroidal anti-inflammatory drugs may serve to augment food-induced reactions and should be noted in the patient’s clinical history.
Although most patients will have rapid symptoms that resolve relatively quickly, a significant minority will have biphasic reactions, defined as a recurrence of symptoms within 72 hours of an initial reaction. An even smaller number of patients may develop refractory or persistent anaphylaxis requiring volume resuscitation and inotropic support.
Current Diet
In addition to classifying food-induced reactions, it is also important to determine which foods a child is currently avoiding. For example, if a patient suspects a distant episode of hives was due to a peanut allergy, the clinician should ask about ingestion of peanut-containing foods since the time of reaction. In cases where the food was previously tolerated and is currently incorporated into the diet, no further testing is warranted. It is noteworthy that some children with food allergies to milk or egg proteins are able to tolerate these foods in extensively heated forms because the IgE molecules in these individuals are likely specific for conformational epitopes, which are denatured during the heating process. As a result, some children may be able to tolerate egg in a muffin but not in an omelet. These children should continue to ingest the allergen in its baked form, as it may signal and hasten the development of oral tolerance. By contrast, IgE to peanuts, tree nuts, and shellfish (among others) are specific for linear epitopes, which are not denatured with heating, and these allergies tend to persist.
Physical Examination
Physical examination of the patient should focus on the signs of an allergic reaction in addition to other atopic disorders commonly associated with food allergies. For example, many patients have comorbid atopic dermatitis. Others may have a history of asthma, which coupled with food allergy increases the risk of mortality from childhood asthma and anaphylaxis. Photographs of acute reactions, if available, may also be helpful. The physical examination may prove useful in distinguishing other conditions with specific findings. It is also important to assess growth parameters in children with food allergy, as this is an established risk factor for growth impairment. Children at special risk include those allergic to milk and/or multiple foods. Consultation with an experienced nutritionist may be considered for all children with food allergy, especially those with poor growth. Speech and feeding therapists may also be called upon to evaluate food-allergic children who may demonstrate dysfunctional feeding behavior.
Immunoglobulin E Mediated Versus Non–Immunoglobulin E Mediated
Although IgE-mediated food allergies are the most common, additional immune-mediated food sensitivities known as eosinophilic gastrointestinal disorders have become increasingly prevalent. Eosinophilic esophagitis (EoE), a disorder characterized by eosinophilic infiltration of the esophageal lining, has emerged as a closely related disease state. In contrast to the rapid symptoms of IgE-mediated food reactions, EoE is defined by a more insidious course resulting in failure to thrive, vomiting, reflux, and food aversion. Constant inflammation of the esophagus may eventually lead to dysphagia, stricture formation, and food impaction in adolescents and adults. Eosinophilic gastrointestinal disorders, however, are not confined to the esophagus and may also involve other segments of the gastrointestinal tract.
Diagnostic testing
Several tools are currently used to assist in the diagnosis of food allergy. Table 2 lists available tools and the settings in which they may be utilized.
| Test | Primary Care Clinic | Allergy Clinic |
|---|---|---|
| sIgE | X | X |
| Full protein | X | X |
| Component a | X | X |
| Skin-prick test | — | X |
| Oral food challenge | — | X |
a The utility of component testing in diagnosing food allergy is still under investigation.
Pediatric Clinic
Specific Immunoglobulin E (ImmunoCAP)
Allergen-specific IgE (sIgE) testing measures the presence of allergic antibody to a particular antigen. This blood test can be performed at any age and is not limited by concurrent antihistamine use. As in many other clinical situations, the detection of an antibody by a highly sensitive but nonspecific immunoassay does not necessarily equate to disease. The presence of sIgE simply denotes allergic sensitization to a particular food protein. Many individuals, especially children with atopic dermatitis, may be sensitized but not clinically allergic. Although sIgE is not routinely recommended for the diagnosis of food allergies, a pediatrician may consider targeted sIgE testing to likely triggers. It is important that this testing be based on a supportive clinical history after ingestion (eg, a high pretest probability of clinical food allergy) and not be ordered indiscriminately. Bird and colleagues recently demonstrated that bulk testing to multiple food antigens with food allergy panels leads to unnecessary cost and dietary restriction. Therefore, if a child tolerates a particular food in his or her diet regularly without clear evidence of allergic disease, sIgE testing should not be ordered. sIgE testing should also not generally be used to screen patients for food allergies before the first ingestion. The application of serologic IgE testing in the diagnosis and management of food allergy patients by primary care physicians has been recently reviewed elsewhere.
Traditionally sIgE has been assessed for an entire food molecule composed of multiple component proteins. Recently, component-resolved diagnostics (CRD) have become available, potentially increasing the sensitivity and specificity of IgE measurements, although this is still being studied. Although CRD for milk, egg, peanut, tree nuts, fish, and shellfish are commercially available, their use is not routinely recommended in food allergy diagnostic guidelines, and many such tests are not covered by insurance carriers. Most of the data supporting CRD come from English and European studies of component IgE testing in peanut-allergic patients, a topic that has been recently reviewed elsewhere.
Allergy Clinic
Skin-prick testing
In addition to sIgE, skin-prick testing (SPT) may be useful in confirming clinical food allergy. SPT is an in vivo assessment of mast cell activation whereby a small amount of allergen is placed in the epidermis. Sensitized patients usually develop a wheal and flare reaction at the site of antigen placement within minutes. Skin reactions are then compared with positive and negative controls, as recent antihistamine use or dermatographism may result in false-negative or false-positive results, respectively. This approach is a safe, rapid, and relatively inexpensive way to assess for food sensitization. In general, SPT has an excellent negative predictive value (NPV; ∼95%) but a poor positive predictive value (PPV; ∼50%).
For those patients who successfully avoid culprit foods and for whom the persistence of food allergy remains uncertain, serial sIgE and SPT may be used to determine whether an oral food challenge is warranted to definitively establish ongoing allergy or tolerance. Table 3 gives general recommendations for the frequency of laboratory monitoring and SPT in children with food allergies. Interpretation of SPT and sIgE must be performed in the appropriate clinical context. Regardless of test values, patients with a recent history of anaphylaxis within the past year should not undergo oral food challenge. Conversely, children who have incorporated a food into their diet without symptoms do not require further testing.
| Allergen | Test | ≤5 y Old | >5 y Old |
|---|---|---|---|
| Milk, egg, wheat, soy, peanut | sIgE, SPT | Every 12–18 mo | Every 2–3 y |
| Tree nuts, fish, shellfish | sIgE, SPT | Every 2–4 y | Every 2–4 y |
Oral food challenge
The double-blinded placebo-controlled food challenge is the gold standard for the diagnosis of food allergy or confirming its persistence. Because of its labor-intensive and time-intensive nature, open food challenges with commercially available food products are usually used in clinical practice. Before performing an oral food challenge (OFC), the patient should understand the risks associated with the procedure and also display an interest in eating the food afterward if he or she passes the challenge. Well-accepted protocols for OFCs have been published but, in general, gradually increasing amounts of a food allergen are administered over successive intervals under close clinical observation. Once a designated quantity is safely consumed, a patient is allowed to incorporate the food into the diet.
Interpretation of test results
Challenge thresholds for interpretation of sIgE and SPT have been established. Table 4 provides the decision points used by many allergists in deciding whether to perform an OFC. These recommendations provide 95% PPV and 50% NPV for reactions to OFCs. A challenge is usually not recommended when sIgE and SPT are greater than 95% PPV. Conversely, a challenge may be considered when the sIgE and SPT are less than 50% NPV. Positive and negative predictive thresholds do not exist for many food allergens, and those listed cannot be extrapolated to antigens such as wheat and soy. These foods typically have much higher sIgE reaction thresholds. It should be noted that most predictive cutoffs were developed using the ImmunoCAP system in children with a high pretest probability of food allergy presenting to a tertiary care allergy subspecialty clinic ; therefore, values generated using other testing platforms cannot be reliably compared with these thresholds. In addition, population-based estimates have shown that these cutoffs may be much higher if testing is performed indiscriminately or in the general population, whereby the tests may detect sensitization more readily than clinical allergy.
