Food Allergy: Practical Considerations for Primary Care

Abstract

Food allergy is increasing in frequency and so is the misunderstanding of what constitutes a true food allergy. This article will review basic concepts of classic IgE reactions to food as well as discuss some that occur through other mechanisms. The importance of a detailed history is emphasized.

Information is provided on optimal evaluation, interpretation of results and treatment of these potentially life-threatening reactions. Finally the role an allergist can play in co-management is discussed.

Introduction

Of all the diseases managed by allergists, one of the most difficult is food allergy. Not only is the incidence increasing, so is the misinformation associated with the disease. With a click of a computer key and the expansion of social networks, more and more information is out there and less and less is critically reviewed. Changing beliefs and providing valid information is not always easy.

In an effort to help clarify a number of issues related to food allergy, “practice parameters”¹ have been published and recently the National Institute for Allergy and Infectious Diseases in December 2010 released its Guidelines for Diagnosis and Management of Food Allergy in the United States.² This consensus statement is the result of the efforts of a number of interested parties, including medical organizations, the federal government and advocacy groups. Although these lengthy documents are available online; it is not known how much they will be used by busy, practicing physicians.

The goal of this article is to review and clarify some basic issues regarding food allergy. Although many of these issues are beyond the scope of this article, it is hoped that this will provide some guidance for primary care doctors as they evaluate food allergies in their office.

The Basics

Surveys have shown that Americans overestimate food allergies. Fifteen to twenty-five percent of Americans consider themselves allergic.³ Studies have shown although the incidence has increased, food allergies occur in up to 8% of children and 3% of adults.⁴ Why is there such a discrepancy? People assume that any reaction to a food must be an “allergy.” This term is rather loosely used to mean anything from indigestion, food poisoning, and even behavior disorders. For purposes of this article, the term “allergy” will refer the classic Gell-Coombs Type I, IgE mediated, immediate hypersensitivity reaction. These are the reactions that can potentially be life threatening and ones for which testing may be available. For review, an IgE mediated reaction first involves the presentation of an antigen (food peptide) by antigen presenting cells to T cells with B cells producing IgE. Formed IgE antibodies bind to mast cells and basophils. With re-exposure food antigens can bind and cross link IgE on these cells resulting in the release of a variety of chemical mediators such as histamine and tryptase that cause classic symptoms such as itching, urticaria, angioedema, vomiting, wheezing, and may progress to hypotension and respiratory arrest.

Obtaining the History

The history is the most important part of making a diagnosis of food allergy. It helps to distinguish between IgE and non IgE mediated mechanisms and helps guide the practitioner on how to best proceed.

A few important points to remember; a true IgE mediated reaction does not happen with first exposure to a food. Sensitization must occur first. An allergic reaction can occur with the second or after multiple exposures. The history obtained should include: types and onset of symptoms; foods and amounts consumed; associated factors; and response to any therapies given.

It is also important to remember that if the mother breast fed for even a short period of time, the infant/toddler may have become sensitized by this route.

This is often the “first” exposure. Once allergic, a reaction should be reproducible every time the food is ingested. The amount may affect the severity but usually not the occurrence of a reaction and for most foods it should not matter how it is prepared. A few exceptions to preparation of some foods will be discussed later. Also, the majority of the reactions usually occur within minutes of ingestion and rarely after two hours. Intolerances usually happen later and may vary with exposures and the amount ingested.

Although symptoms can occur in a variety of organ systems (See Table 1), they usually occur where there is first contact with the food; (cutaneous) with flushing, itching, hives and/or swelling around the mouth ;(gastrointestinal) swelling of the tongue, vomiting, and may progress to (respiratory) difficulty swallowing, wheezing, hypotension and respiratory arrest. The most common symptoms seen are hives, itching, mild swelling and vomiting.⁵

Table 1.

Allergic Symptoms

Organ	Symptoms
Skin	urticaria, flushing, angioedema, pruritus
Gastrointestinal (GI)	oral itching, tongue swelling, vomiting, abdominal pain, cramping
Respiratory (upper)	sneezing, rhinorhea, hoarseness, itching
(lower)	coughing, wheezing, dyspnea, cyanosis
Cardiovascular	Hypotension, tachycardia, bradycardia, cardiac arrest

It should be noted that although rhinorrhea may be seen with other symptoms in an acute allergic reaction, food allergy is not associated with chronic rhinitis symptoms.

Symptoms limited exclusively to the GI tract are less likely pure IgE mediated and more often related to an intolerance, other non IgE mechanisms or from some other adverse reaction. These may include such things as lactose intolerance, protein intolerance, or celiac disease. The mechanisms involved in Eosinophilic Gastritis/Gastroenteritis are thought to possibly be IgE and non IgE mediated. Table 2 lists some other diseases often mistaken as an IgE food allergy.

Table 2.

Adverse Reactions to Foods

Non IgE Mediated Diseases Protein Intolerance ♦ Enterocolitis ♦ Protein Enteropathy ♦ Protein Enterocolitis Celiac Disease/Dermatitis Herpetiformis Heiner’s Syndrome Disaccharidase Deficiencies/ Metabolic Auriculotemporal Syndrome Gustatory Rhinitis GI Disorders: pyloric stenosis, pyloric stenosis, TE fistula, cystic fibrosis, malabsorption, peptic ulcer, GE reflux Metabolic disorders: Galactosemia, phenylketinuria Pharmacologic: jitteriness (caffeine), headache (tyramine), pruritus (histamine)/Toxic (spoiled fish) Psychologic disorders: phobias/ aversions Gallbladder/liver disease; hiatal hernia Mixed IgE and Non IgE Mechanisms Eosinophilic Esophagitis Eosinophilic Gastroenteritis Atopic Dermatitis Contact Dermatitis

As can be seen there are quite a few non IgE Mediated reactions that need to be considered. This article can not discuss all of them, but Table 3 reviews a few of the most common.

Table 3.

Distinguishing Clinical Features /Non IgE Mediated

Symptoms	Disease
	Proctocolitis	Enterocolitis	Enteropathy	Celiac Disease
Vomiting	Absent	Prominent	Variable	Variable
Diarrhea	Minimal (bloody)	Prominent	Moderate (may have edema)	Variable
Growth	Normal	Poor	Poor	Poor
Foods	Breast, Milk, Soy	Milk, Soy	Milk, Soy	Gluten
Onset	Days to 6 mo.	Days to 1 yr severe with re-exposure	2 – 24 mo.	> 4 mo.

Adapted from Leung DYM, Sampson HA, Geha R, Szefler SJ. Pediatric Allergy Practice and Principles. 1st ed. New York. Saunders. 2003.

There specifically seems to be much confusion surrounding Celiac Disease. This is caused by an immune response to Gliadin (alcohol soluble portion of gluten) in wheat, rye, barley. This is not an allergy to wheat as is often thought and IgE testing is of no benefit. Antibodies often found include: IgA anti transglutaminase; IgA anti-gliadin, and antiendomysium antibodies. This disease is best managed by a gastroenterologist.

Although there is much in the lay press relating food allergies to behavioral, learning, or psychological issues, there have been no good well designed, blinded studies proving a link. Although specific IgE testing is available for foods, a positive result does not prove cause and effect.

Evaluation

Two tests are available to help identify an IgE mediated food allergy: a prick skin test and/or blood test measuring specific IgE. The ImmunoCap system for measuring specific IgE has been the preferred method used in many of the clinical trials for food allergy. Both tests have pros and cons but are similar in specificity, although the skin test is slightly more sensitive.² Prick skin tests can provide results within 15 minutes and are less expensive. Blood testing can be done when skin testing is not possible such as with the use recent use of an antihistamine; with significant eczema, and/or dermatographism.

The history is the most important part in evaluating a suspected food allergy. A positive test is not enough to make a diagnosis. There must be a history of allergic symptoms as well. Prick skin test and blood test for specific IgE have a high false positive rate; up to 50 percent when there is no convincing history.² Therefore, these are poor screening tests by themselves. A negative result is more helpful in excluding an allergy. If either is negative the risk of reacting is overall is very low, but still not zero. Because of the high rates of false positives, food panels should not be used. These have lead to an over diagnosis of food allergy and often to unnecessary food restrictions. Testing should be done only to the suspect food if one can be identified.

At this time, there is no evidence that IgG levels to food are of any benefit in making a diagnosis. They are thought only to represent exposure to foods that have been ingested. The European Academy of Allergy and Clinical Immunology has published a position statement against the use of IgG and IgG4 for diagnosing food allergy.⁶ The physical exam is usually not helpful in making a diagnosis of food allergy. Most patients see the practitioner when they are asymptomatic. The exam may show evidence of atopy, but there is nothing pathognomonic.

If there is a convincing history and a positive test, a presumptive diagnosis may be made. If the history is questionable or a positive test alone is the only evidence for a reaction, then an Oral Challenge can and often should be performed. A double blinded, placebo controlled oral challenge is considered the “Gold Standard “for diagnosing a food allergy.⁷

Although single or double blinded challenges can be used, these are likely employed when there is great fear about a specific food or when trying to prove something other than an IgE reaction is responsible for the symptoms. Most often an open challenge is used. Small amounts of the suspect food are given and increased usually over 20–30 minutes until the equivalent of a prescribed serving has been consumed. The patient is observed closely for symptoms during each phase. The challenge proceeds if no symptoms are observed and an additional observation period is used after the last dose has been given. If the food is tolerated and no IgE mediated symptoms are observed, then a true food allergy is ruled out. Verifying symptoms also helps prove that an allergy exists.

Oral challenges require cooperation of the patient. If a young child will not cooperate with the stepped challenge, it can not be done. Oral challenges are more often used to demonstrate loss of a food allergy, when time and testing would make it more likely an allergy has been outgrown.

Although any food can cause a reaction, approximately ninety percent of all food allergies are caused by six foods: milk, egg, wheat, soy, peanut and fish in kids. In adults, tree nuts and shellfish are more common.⁸ For food allergies that patients can “outgrow,” repeat IgE testing is used to follow a loss of specific IgE to a food.

Table 4 lists decision points for some common foods. These values are unique for each food. Values of specific IgE at or above the decision point for at least four common foods would indicate > ninety-five percent of patients challenged would react. For prick skin testing to foods, studies would suggest that a mean wheal diameter > 8mm would increase the risk of a reaction.⁹ As is seen, the probability of a reaction is unique for each food. “Class” designations reported with IgE testing may not be helpful in evaluating risk of reaction.

Table 4.

Prediction of Reaction to some Common Foods

Food	Food-specific IgE concentration	Positive Predictive Value
	at or above which clinical reaction is likely (kU/L)
Milk	15	95
infants < 1	5	95
Egg	7	98
Infants < 2	2	95
Peanut	14	99
Codfish	20	99
Soy	30	73
Wheat	26	74

Adapted from Sampson HA, Ho DG. Relationship between food-specific IgE concentrations and the risk of positive food challenges in children and adolescents. J allergy Clin Immunol 1997;100:444–451. Sampson HA. Utility of food-specific IgE concentrations in predicting symptomatic food allergy. J Allergy Clin Immunol 2001;107:891–896.; Boyano MT, et al Clin Exp Allergy 2001;31:1464–69.; Garcia-Ara C, et al. J Allergy Clin Immunol 2001;107:185–90.

In following patients for loss of a food allergy, repeat prick skin tests are not usually done as they may often remain positive (often less) even when an allergy has been lost. In deciding to perform an oral challenge, the specific IgE should be at a very low level compared with the decision point or as close to Class 0 (0.35 kU/L) as possible. A decision to retest is often based on the chance of losing an allergy, the initial size of the skin test/level of specific IgE, and the natural history of that specific allergen if known.

A few caveats need to be mentioned in regards to food allergy. In patients with eczema, they may have classic immediate IgE reactions; however, their only manifestation of food allergy may be just a worsening/flare of eczema symptoms temporally related to ingestion of the offending protein. This is often investigated by a single elimination of the suspected protein in all forms for two to three weeks. There should be a significant decrease in symptoms during this time and a significant flare of the eczematous rash or urticaria shortly after its’ reintroduction. If there is no change, there is no reason to avoid the food for eczema. This would indicate a false positive test.

Oral Allergy Syndrome (Pollen-Food Syndrome) is a unique manifestation of food allergy. The mechanisms are not known. These patients usually describe localized symptoms in their mouth with the ingestion of the offending food. These symptoms are usually itching, burning, and or swelling. These patients will have positive testing to the food in question but very rarely do symptoms progress. They also have IgE antibodies to aeroallergens. The foods implicated are often fresh fruits and vegetables (usually not cooked) that are known to cross react with certain pollens. Classic examples include: melon and ragweed and birch tree pollen and apple.

This is little evidence that artificial dyes and preservatives produce a true allergic reaction.¹⁰ There are however two protein based, naturally occurring dyes used in the food industry that can cause an IgE mediated reaction.^11,12 Annato, derived from a seed, is used to provide yellow/orange color especially with cheeses. Carmine is a red dye derived from insects (Dactulopius coccus costa). Specific IgE testing is available.

Lastly, a word or two about baked egg and milk protein. It has been shown that extensive heating such as baking of milk and egg protein can alter the confirmation of the protein and in some patients make these less allergenic. There are some egg allergic patients who report tolerating baked eggs such as in muffins but not able to tolerate quickly cooked scrambled eggs. Recent studies show these patients may safely eat extensively heated products while avoiding milk and eggs in other forms.^13,14 This does not appear to delay loss of food allergy in these patients. In others, all forms may be allergenic. In allergic patients who have never eaten baked products, it is suggested that they avoid all forms of milk and egg. Additional testing and oral challenges may be used to try to distinguish between these patients.

There is always concern about the risk of reactions to similar or related foods. Table 5 provides data on the risk of some common foods.

Table 5.

Cross Reactivity of Some Common Foods

If Allergic To	Risk of Reaction To	Percent
Cow’s Milk	Goat’s Milk	92%
Peanut	Another Legume	5%
Cow’s Milk	Beef	10%
Grain	Another Grain	20%
Fish	Another Fish	50%
Shellfish	Another Shellfish	75%

Adapted from: Sicherer SH. Clinical Implications of cross-reactive food allergens. J Allergy Clin Immunol. 2001;108:881–890.

Although peanuts do not cross react with tree nuts, it is usually recommended to avoid all nuts or peanuts if allergic to either because of the risk of cross contamination that often occurs in the food industry. Plain labeling is required by law for the major food allergens. A variety of other, often confusing labels list a possibility of contamination but the risk is unknown.

Risk Factors

Although it is a common misconception, allergies to specific foods are not inherited directly. It may be coincidental that members of a family may have a similar allergy. More importantly, the risk in general of having any atopic disease (asthma, food allergy, eczema, allergic rhinitis) is increased if either parent is atopic and if the patient already has some type of atopic disease.¹⁵

Anaphylaxis

An incorrect, commonly held belief is that reactions to foods get worse with each ingestion. Food reactions are often stereotypic. Even so, studies have shown that reactions cannot be predicted. Since many factors can affect a reaction such as age, degree of sensitization, form of the food, amount, rate of absorption among other¹⁵ each reaction must be dealt with individually. Near fatal and fatal anaphylaxis have been associated with underlying asthma, delay in using epinephrine, certain foods (shellfish, nuts), teen years, lack of initial cutaneous reactions, and a biphasic reaction.¹⁶

Treatment

At present, the treatment for any food allergy is strict avoidance. Unlike allergic rhinitis, there is no proven, FDA approved immunotherapy presently available although ongoing research is offering new hope. For foods in which an allergy can be lost, periodic re-evaluation of specific IgE and oral challenges are recommended when appropriate.

It is essential that persons with food allergies also have an “Emergency Food Plan,” detailing symptoms to look for, instructions for dosing medications, and when to seek emergency help. A downloaded form is available thorough the Food Allergy and Anaphylaxis Network at www.Foodallergy.org. Medications needed include a quick acting antihistamine such as diphenhydramine (for mild reactions) and injectable epinephrine for symptoms suggesting a more severe reaction or anaphylaxis. Studies have shown up to 20% of patients may need more than one dose of epinephrine for recovery, so it is advisable to prescribe two doses. This plan and medications should always be readily available; and the patient/responsible adult needs to know when and how to administer the medications and when to seek emergency care.

Prevention

Although recommendations have varied through the years, delaying the introduction of more allergenic foods into an infant’s diet, restricting the mother’s diet during pregnancy or during nursing have not been shown to prevent food allergy. ¹

New Therapy on the Horizon?

Presently, there are a number of ongoing clinical trials aimed at developing additional therapies to decrease the risk of symptoms with accidental exposure, to desensitize patients to a particular food and to induce tolerance. Experiments with Chinese herbal medicine; protocols giving small, incremental amounts of an allergenic food; or sublingual immunotherapy to patients over many months have offered some insight into what may be possible in the future.¹⁷ However, none of these treatments are ready for general use.

When to Refer

An allergist can offer invaluable help with patients with food allergies. If the history is straight forward and reliable testing is available; a diagnosis can often be made and initial therapy started by the primary care doctor. Even when this occurs, it is wise to refer as the patient/family often still have many questions related to prognosis, cross reactivity, emergency treatment plans, and repeat testing. For complicated patients, it is often best to have the patient avoids suspected foods, provide an emergency plan and refer on for further evaluation and testing. In addition to skin tests or specific IgE testing, this evaluation may include completion of food logs, collection of labels from processed foods, lists of ingredients in restaurant foods, and a series of separate oral challenges may be required. This is often time consuming and not without risks. An allergist and his staff have the knowledge, testing capabilities, and time to evaluate, educate and manage all aspects of this disease.

Long Term Prognosis

Some food allergies, such as milk and egg, are more likely to be outgrown. Usually 80% of patients with these two most common food allergies lose their sensitivity over time. Previously, this was thought to occur by school age. Recent studies would suggest that for egg it may not occur in the majority until teenage years.¹⁸ Some food allergies are likely to be life long such as shellfish and tree nuts. Although peanut allergy is more likely to persistent in most patients, approximately twenty percent may lose their sensitivity over time.¹⁹

Take Home Points.

• A detailed history of the reaction and any subsequent reactions is crucial. Test only for foods that you believe maybe implicated.

• If a food may be eaten without symptoms, a food allergy does not exist.

• Avoid using panels. Individual specific IgE measures are available for most common foods.

• There is a high false positive rate to any food tested without a history of classic IgE mediated symptoms. A negative skin or blood tests is more helpful in ruling out a food allergy but is not 100%. Patients still may react with negative tests.

• The size of the skin test or level of specific IgE does not correlate with the severity of a reaction, but does with the likelihood any reaction will occur

• It is rare to truly be allergic to multiple foods; most persons have up to three food allergies.

• If the history is not straight forward seek the help of an allergist.

• Proving and disproving a true allergy may require an office supervised oral challenge (open or blinded) and this is oft en required to evaluate that an allergy no longer exists.

• A food allergy emergency plan, a medical alert bracelet. and rescue medications should always be readily available.

• If the symptoms are mild an anti histamine may be all that is needed to treat a reaction; however, if more than one organ symptom is involved (Table 2) and/or any signs of respiratory/ cardiovascular compromise, injectable epinephrine should be used and emergency care should be sought.

Biography

Paul J. Dowling, MD, is Director, Allergy/Immunology Training Program, Associate Professor, Department of Pediatrics at the University of Missouri – Kansas City School of Medicine and is in the Section of Allergy/Asthma/Immunology at Children’s Mercy Hospitals and Clinics in Kansas City.

Contact: pdowling@cmh.edu