A thorough clinical reaction history must be used to focus the diagnostic workup and identify the causative food involved. This history is then combined with tests for the presence of immunoglobulin E (IgE) to rule out non-immunologic reactions such as food intolerance (see Figure 1).10
All diagnostic workups should begin with a detailed medical history, including all foods eaten prior to the reaction, symptoms, time taken to react, and response to medications. Symptoms typically occur within minutes to a few hours, but in some cases, onset may be delayed or a child may have a biphasic reaction.10
Cutaneous symptoms such as erythema, pruritis, urticaria, morbilliform eruption, angioedema, eczematous rash, and flushing are commonly recognized as symptoms of food allergy. It is important to recognize, however, that many present without cutaneous symptoms. Other signs and symptoms of food allergy may include ocular symptoms (eg, pruritis, periorbital edema, tearing, conjunctival erythema); respiratory symptoms (eg, nasal congestion, pruritis, rhinorrhea, sneezing, hoarseness, dry staccato cough, chest tightness, dyspnea, wheezing, intercostal retractions, accessory muscle use); gastrointestional symptoms (eg, angioedema of the lips, tongue or palate, oral pruritis, tongue swelling, nausea, colicky abdominal pain, reflux, vomiting, diarrhea); and cardiovascular symptoms (eg, tachycardia, hypotension, dizziness, fainting, loss of consciousness).10 The symptoms may vary depending on the type of allergen, the child’s sensitivity to the allergen, and the amount of allergen the child has ingested.
Food-induced anaphylaxis is a severe allergic reaction that is rapid in onset and may lead to death.12 Although cutaneous symptoms occur in many food-allergic reactions, they are less common in food-induced anaphylaxis. Anaphylaxis typically presents with hypotension or involvement of any two organ systems: involvement of skin-mucosal tissues (eg, hives, itching, flushing, swollen lips, tongue, or ulva), respiratory compromise (eg, dyspnea, wheeze, bronchospasm, stridor, hypoxemia), hypotension or associated symptoms of end-organ dysfunction (eg, hypotonia, syncope, incontinence), or persistent gastrointestional symptoms (eg, crampy abdominal pain, vomiting).12 Anaphylaxis typically occurs within seconds to minutes, although death may occur up to 2 hours after the exposure.10,12
Severity of the next food-allergic reaction cannot be predicted by the severity of past reactions nor by the magnitude of one’s skin or blood test (eg, higher scores do not necessarily indicate a more severe allergy).10 Even a seemingly mild reaction has the potential to quickly progress to anaphylaxis. Progression to a severe reaction can be avoided by recognition and prompt treatment. It is thus imperative that physicians prescribe medications for both mild and severe reactions even if the child has never had a severe reaction in the past.
Pediatricians may use allergen-specific serum immunoglobulin E (IgE) tests to confirm suspected cases of food allergy when indicated by reaction history.10 Other recommended diagnostic tests that an allergist will use include the skin prick test and the oral food challenge.10 Atopy patch testing, intradermal food testing, IgG4 food testing, and total IgE levels are not recommended for diagnosing food allergy.10
Allergen-Specific Serum IgE Tests
The only diagnostic tests for food allergy currently available to pediatricians are allergen-specific serum IgE tests. These tests detect the presence of IgE antibodies in response to a particular allergen in a sample of the patient’s blood.10 The patient’s allergen-specific IgE level should be compared to diagnostic “cutoff” levels, which refer to the concentration of allergen-specific IgE that is predictive of a true allergy. Such cutoff levels vary by allergen, brand, assay system, and are lower for younger children.13,14 Ninety percent cutoff levels have been determined in the research literature.14
For example, if the patient has a peanut-specific IgE level that is higher than the 90% cutoff level for peanut, we can be more than 90% certain that the patient has a true peanut allergy. Conversely, using cutoff levels with such a high predictive value also means that children with true allergies but low allergen-specific IgE levels will be missed or not diagnosed. For this reason, a much lower IgE concentration of 0.35 kU/L (the lowest detection limit of the test) has been used in clinical practice as a general cutoff level.
This general cutoff level predicts a true milk allergy 68% of the time, egg allergy 67% of the time, peanut allergy 76% of the time, soy allergy 78% of the time, and wheat allergy 100% of the time.15 Recently, improved IgE tests can detect levels as low as 0.1 kU/L, which is starting to become the new general cutoff level.16
Diagnostic testing must be guided by reaction history, as opposed to testing for all common food allergens with a food allergy panel. In particular, use of laboratory-offered standard panels (ie, panels evaluating multiple common allergens) is discouraged due to the high rate of false-positive results.17–20 In short, if a child is currently consuming a food without symptoms, diagnostic testing for that food is not warranted. A positive test result in the absence of symptoms does not indicate a true allergy; a child can have high allergen-specific serum IgE levels without being truly food-allergic.17–20 Misinterpretation of diagnostic testing results without a corroborating reaction history may lead to unnecessary dietary restrictions, which has the potential to adversely affect nutrition21 as well as the family’s quality of life.22
Therefore, it is critical that physicians selectively use diagnostic testing only when indicated by reaction history.17–20
Conversely, children with true food allergy may have undetectable IgE levels. In cases where the reaction history is highly suggestive, evaluation by an allergist is necessary before notifying both the parent and the child that he or she may ingest the suspected food.
Skin Prick Tests
Skin prick tests (SPT) are currently only performed by allergy or immunology specialists. This test detects the presence of IgE bound to cutaneous cells rather than free IgE in the blood.10 Hence, skin and blood testing may not always show the same results. A positive result is defined as a wheal with a mean diameter of at least 3 mm or a diameter that is greater than the negative (diluent) control.23 Similar to interpretation of blood test results, positive skin test results should be interpreted cautiously due to its high rate of false-positive results.
Oral Food Challenges
Oral food challenges (OFC) are also only performed by specialists in allergy or immunology. The procedure involves incremental feeding of the suspected food allergen.10 Any reaction during an OFC is considered a positive test result. A positive oral food challenge result is diagnostic of food allergy, regardless of skin or blood test results.
Tolerance Development Testing
Milk, egg, and peanut account for the vast majority of food allergy in young children.1 Many children with milk, egg, soy, or wheat allergy eventually outgrow their allergy.10 More than half of children outgrow their milk allergy by 12 years of age, and egg allergy by 14 years of age, soy allergy by 10 years of age, and wheat allergy by 8 years of age.24–27 To this end, follow-up testing for tolerance is reasonable annually for milk, egg, soy, or wheat allergy.
Teenagers and adults, on the other hand, are most commonly allergic to peanut, tree nut, and shellfish.10 Peanut, tree nut, and shellfish allergies will typically persist into adulthood.10 Only 22% of children will outgrow peanut allergy,28 and less than 10% of patients will outgrow tree nut allergy.29 Thus, testing for these allergens can be repeated less frequently (eg, every 2 to 3 years) depending on the reaction history.
A decrease in allergen-specific IgE levels is often a marker for the onset of tolerance.25–28,30–32 However, a child may have decreased IgE levels without truly outgrowing the allergy. Hence, tolerance must be confirmed with an oral food challenge (by allergists) prior to telling the parents that the child is no longer allergic and may ingest the food. After confirming development of tolerance, the child should consume the outgrown allergen on a regular basis to avoid recurrence of the allergy.33