Food Allergies

Synonyms and related keywords: adverse immunologic reactions to foods, allergic reactions to foods, food hypersensitivity, food intolerance, adverse food reactions, lactose intolerance, bacterial food poisoning, peanut allergy, protein-induced enterocolitis syndrome, food hypersensitivity, allergen exposure, anaphylactic reactions, food-induced anaphylactic reaction, oral allergy syndrome, dietary protein enterocolitis, food-induced asthma, food-induced pulmonary hemosiderosis, Heiner syndrome, egg allergy, milk allergy, peanut allergy, soy allergy, fish allergy, shellfish allergy, tree nut allergy, wheat allergy



INTRODUCTION

Background

Adverse food reactions can be broadly classified into 2 categories. The first category consists of immunologically-mediated adverse reactions to foods; these reactions are unrelated to any physiologic effect of the food or food additive. These reactions include disorders mediated by immunoglobulin E (IgE) antibodies (eg, IgE-mediated reaction to peanuts), which begin during or soon after exposure to the food, and others resulting from non–IgE-mediated mechanisms (eg, non–IgE-mediated reactions such as protein-induced enterocolitis syndrome), which generally take several hours to evolve.

The second category is food intolerance. These reactions include any adverse physiologic response to a food or food additive that is not immunologically mediated (eg, lactose intolerance, bacterial food poisoning).

Pathophysiology

Allergic reactions to food are IgE-mediated or non–IgE-mediated. Immune responses mediated by specific IgE antibodies are the most widely recognized mechanism of food hypersensitivity. Patients with atopy produce IgE antibodies to specific epitopes of the food allergen. These antibodies bind to high-affinity IgE receptors on circulating basophils and tissue mast cells present in the skin, gastrointestinal tract, and respiratory tract. Subsequent allergen exposure binds two adjacent IgE antibodies, resulting in receptor cross-linking and intracellular signaling that initiates the release of numerous mediators, including histamine, prostaglandins, leukotrienes, chemotactic factors, and cytokines. The effects of these mediators on surrounding tissues result in vasodilatation, smooth muscle contraction, and mucus secretion, which, in turn, are responsible for the spectrum of clinical symptoms observed during allergic reactions to food.

Food allergens are typically water-soluble glycoproteins resistant to heating and proteolysis with molecular weights of 10-70 kd. These characteristics facilitate the absorption of these allergens across mucosal surfaces. Numerous food allergens are purified and well-characterized, such as peanut Ara h1, Ara h2, and Ara h3; chicken egg white Gal d1, Gal d2, and Gal d3; soybean-Gly m1; fish-Gad c1; and shrimp-Pen a1. Closely related foods frequently contain allergens that cross-react immunologically (ie, lead to the generation of specific IgE antibodies detectable by skin prick or in vitro testing) but less frequently cross-react clinically. Finally, cross-reactive allergens have been identified among certain foods and airborne pollens (see Pollen-food allergy syndrome). Conserved homologous proteins shared by pollens and foods likely account for this cross-reactivity.

Frequency

United States

General surveys report that as many as 25-30% of households consider at least 1 family member to have a food allergy. This high rate is not supported by controlled studies in which food challenges are used to confirm patient histories. The actual prevalence of food allergies is estimated to be approximately 6% in infants and children and 3.7 % in adults. Several published prospective investigations have determined the prevalence of certain common food allergies in children (eg, cow milk, 2.5%; eggs, 1.3%; peanuts, 0.8%; wheat, 0.4%; soy, 0.4%).

International

Prospective studies from several different countries indicate that approximately 2.5% of newborn infants experience hypersensitivity reactions to cow milk in the first year of life. A hypersensitivity reaction to peanuts occurs in approximately 0.5% of children in the United Kingdom. Surveys from the United Kingdom indicate that 1.4-1.8% of adults experience adverse food reactions and 0.01-0.23% of adults are affected by adverse reactions to food additives. Studies from the Netherlands demonstrate that approximately 2% of the adult Dutch population is affected.

Mortality/Morbidity

• Severe anaphylactic reactions, including death, can occur following the ingestion of food. Typical symptoms observed in a food-induced anaphylactic reaction involve the skin, gastrointestinal tract, and respiratory tract. Frequently observed symptoms include oropharyngeal pruritus, angioedema (eg, laryngeal edema), stridor, dysphonia, cough, dyspnea, wheezing, nausea, vomiting, diarrhea, flushing, urticaria, and angioedema. Fatalities result from severe laryngeal edema, irreversible bronchospasm, refractory hypotension, or a combination thereof. Food allergy has been confirmed in approximately one third of the patients with anaphylaxis presenting to the emergency department at the Mayo Clinic.



• Peanuts, tree nuts, and shellfish are the foods most often implicated in severe food-induced anaphylactic reactions, although anaphylactic reactions have been reported to a wide variety of foods.



• Risk factors for fatal food-induced anaphylaxis include (1) the presence of asthma, especially in patients with poorly controlled disease; (2) previous episodes of anaphylaxis with the incriminated food; (3) a failure to recognize early symptoms of anaphylaxis; and (4) a delay or lack of immediate use of emergency medications (eg, epinephrine, antihistamines) to treat the allergic reaction.

Race

• No predilection is known.

Sex

• No predilection is known.

Age

• In infants and children younger than 3 years, the prevalence of food allergy is approximately 6%.



• The estimated prevalence in adults is approximately 3.7%.

CLINICAL

History

• Necessary elements of a thorough medical history
  
  
  • Develop a complete list of all foods suspected to cause symptoms.
  
  
  
  • Discuss the manner of preparation of the food (cooked, raw, added spices or other ingredients).
  
  
  
  • Determine the minimum quantity of food exposure required to cause the symptoms.
  
  
  
  • Determine the reproducibility of symptoms upon exposure to the food.
  
  
  
  • Obtain a thorough description of each reaction, including the following:
    
    
    • The route of exposure (ingestion, skin contact, inhalation, injection) and dose
    
    
    
    • The timing of the onset of symptoms in relation to food exposure
    
    
    
    • All observed symptoms and each one’s severity
    
    
    
    • The duration of the reaction
    
    
    
    • The treatment provided and the clinical response to treatment
    
    
    
    • The most recent reaction
      
  • Inquire about a personal or family history of other allergic disease.
    
• Cutaneous reactions
  
  
  • These are the most common clinical manifestations of an allergic reaction to a food or food additive.
  
  
  
  • Symptoms range from acute urticaria (most common) to flushing to angioedema to exacerbations of atopic dermatitis.
  
  
  
  • Food allergy is rarely the cause of chronic urticaria or angioedema.
    
• Atopic dermatitis
  
  
  • Significant controversy surrounds the role of food allergy in the pathogenesis of atopic dermatitis. Studies show that of patients with moderate chronic atopic dermatitis, 35-40% have IgE-mediated food allergy contributing to their skin disease.
  
  
  
  • Both food-specific IgE-mediated and cellular mechanisms appear responsible for chronic eczematous inflammation.
  
  
  
  • Removal of a specific food allergen leads to reduction or resolution of clinical symptoms in affected patients; reintroduction of the food exacerbates the atopic dermatitis. Reintroduction of a suspected food allergen should be performed under medical supervision because, in some instances, initial reintroduction of the food after a period of dietary elimination has resulted in more significant symptoms than were observed when the food was regularly ingested.
  
  
  
  • Prophylactic studies show that avoiding particular foods (eg, cow milk, eggs, peanuts) helps delay the onset of atopic dermatitis.
    
• Dermatitis herpetiformis
  
  
  • This is an unusual form of non-IgE cell-mediated hypersensitivity related to celiac disease. It manifests clinically with a chronic and intensely pruritic rash with a symmetrical distribution that has some similarities to the typical rash distribution of atopic dermatitis.
  
  
  
  • Elimination of gluten from the diet usually leads to resolution of skin symptoms.
    
• IgE-mediated gastrointestinal food allergy
  
  
  • These food allergy reactions include immediate hypersensitivity reactions and the pollen-food allergy syndrome (oral allergy syndrome).
  
  
  
  • Specific gastrointestinal symptoms include nausea, vomiting, abdominal pain, and cramping. Diarrhea is found less frequently.
    
• Pollen-food allergy syndrome (Oral allergy syndrome)
  
  
  • Patients with this syndrome develop itching or tingling of the lips, tongue, palate, and throat following the ingestion of certain foods. In addition, edema of the lips, tongue, and uvula and a sensation of tightness in the throat may be observed. In fewer than 3% of cases, symptoms progress to more systemic reactions, such as laryngeal edema or hypotension.
  
  
  
  • This syndrome is caused by cross-reactivity between certain pollen and food allergens. For example, individuals with ragweed allergy may experience oropharyngeal symptoms following the ingestion of bananas or melons, and patients with birch pollen allergy may experience these symptoms following the ingestion of raw carrots, celery, potato, apple, hazelnut, or kiwi.
    
• Mixed IgE/non-IgE gastrointestinal food allergy (eosinophilic gastroenteritis)
  
  
  • Typical symptoms include postprandial nausea, abdominal pain, and a sensation of early satiety.
  
  
  
  • One of the hallmarks in children is weight loss or failure to thrive.
  
  
  
  • CBC count and differential findings may show eosinophilia in approximately 50% of patients; however, this is not diagnostic. Typically, endoscopy and biopsy must be performed in order to establish the presence of eosinophils in the intestinal wall. While a dense eosinophil infiltrate may be seen anywhere from the lower esophagus throughout the large bowel, involvement is patchy and variable.
  
  
  
  • Ultimately, an elemental or oligoantigenic diet is necessary to aid in the diagnosis.
  
  
  
  • If the patient does not respond to the elemental diet, a trial of systemic oral corticosteroids can be useful for resolving the clinical symptoms.
    
• Non–IgE-mediated gastrointestinal food allergy
  
  
  • Dietary protein enterocolitis is a syndrome that typically manifests in the first few months of life in a child who has severe projectile vomiting, diarrhea, and failure to thrive.
  
  
  
  • Cow milk and soy protein formulas are usually responsible for these reactions, which occur 2 or more hours after food ingestion.
  
  
  
  • Infants typically appear lethargic, wasted, and dehydrated. To establish the diagnosis, an oral challenge study must be performed.
    
• Upper and lower respiratory tract reactions
  
  
  • Upper respiratory reactions typically include nasal congestion, sneezing, nasal pruritus, or rhinorrhea. They are usually observed in conjunction with ocular, skin, or gastrointestinal symptoms.
  
  
  
  • IgE-mediated pulmonary symptoms may include laryngeal edema, cough, or bronchospasm.
    
• Asthma
  
  
  • The role of food allergy in the pathogenesis of asthma is a controversial area of investigation.
  
  
  
  • At the National Jewish Center for Immunology and Respiratory Medicine, 67 of the 279 children (24%) with a history of food-induced asthma were documented to have a positive result after a blinded food challenge, which included wheezing. Interestingly, only 5 (2%) of these patients had wheezing as their only objective adverse symptom.
  
  
  
  • In a related report, 320 children with atopic dermatitis undergoing blinded food challenges at Johns Hopkins Hospital were monitored for respiratory reactions. Overall, 34 of 205 (17%) children with positive results from food challenges developed wheezing as part of their reaction. Therefore, a conservative estimate is that 5-10% of patients with asthma have food-induced allergy symptoms.
  
  
  
  • In a pediatric case-controlled study comparing 19 children who required ventilation for an exacerbation of asthma and 38 control subjects matched by sex, age, and ethnicity, coincident food allergy was found to be independently associated with life-threatening asthma.
  
  
  
  • Wheezing as the only manifestation of an allergic reaction to food is rare.
  
  
  
  • Children with atopic dermatitis, especially those with food reactions confirmed during blinded food challenges, appear to have a higher risk for developing food-induced asthma.
  
  
  
  • The primary clinical effect is not acute bronchopulmonary obstruction, but chronic asthma symptoms or difficulty in controlling the asthma.
    
• Food-induced pulmonary hemosiderosis (Heiner syndrome)
  
  
  • This is a rare disorder characterized by recurrent episodes of pneumonia associated with pulmonary infiltrates, hemosiderosis, gastrointestinal blood loss, iron deficiency anemia, and failure to thrive in infants.
  
  
  
  • While the precise immunologic mechanism is unknown, it is thought to be secondary to a non-IgE hypersensitivity process.
    
• Food-induced anaphylaxis
  
  
  • Following the ingestion of food, severe anaphylactic reactions (ie, systemic allergic reactions), including death, can occur.
  
  
  
  • Symptoms may include the following:
    
    
    • Oropharyngeal pruritus
    
    
    
    • Angioedema (eg, laryngeal edema)
    
    
    
    • Urticaria
    
    
    
    • Ocular injection, ocular pruritus, conjunctival edema, periocular swelling
    
    
    
    • Nasal congestion, nasal pruritus, rhinorrhea, and sneezing
    
    
    
    • Stridor
    
    
    
    • Dysphonia
    
    
    
    • Cough
    
    
    
    • Dyspnea
    
    
    
    • Wheezing, bronchospasm
    
    
    
    • Nausea
    
    
    
    • Emesis
    
    
    
    • Abdominal pain
    
    
    
    • Diarrhea
    
    
    
    • A feeling of impending doom
    
    
    
    • Cardiovascular collapse
      
  • Risk factors for fatal reactions include the following:
    
    
    • The presence of asthma, especially in patients with poorly controlled disease
    
    
    
    • Previous episodes of anaphylaxis with the incriminated food
    
    
    
    • Failure to recognize early symptoms of anaphylaxis
    
    
    
    • Delay or lack of immediate use of emergency medications (eg, epinephrine, antihistamines)

Physical

• The physical examination findings are most useful for assessing overall nutritional status, growth parameters, and signs of other allergic disease, such as atopic dermatitis, allergic rhinitis, or asthma.



• Findings from a comprehensive physical examination can help rule out other conditions that may mimic food allergy.

Causes

• Any food protein can trigger an allergic response, and allergic reactions to a large number of foods have been documented; however, only a small group of foods account for most of these reactions.



• Eggs, milk, peanuts, soy, fish, shellfish, tree nuts, and wheat are the foods most often implicated in allergic reactions that have been confirmed in well-controlled blinded food challenges.



• Investigations of near-fatal or fatal anaphylactic reactions following food ingestion reveal that most are caused by peanuts, tree nuts, and shellfish.

DIFFERENTIALS

Anorexia Nervosa
Bulimia
Celiac Sprue
Clostridium Difficile Colitis
Constipation
Diverticulitis
Dumping Syndrome
Esophageal Motility Disorders
Esophageal Spasm
Esophageal Stricture
Esophagitis
Factitious Disorder
Food Poisoning
Gastritis, Acute
Gastritis, Chronic
Gastroenteritis, Bacterial
Gastroenteritis, Viral
Gastroesophageal Reflux Disease
Giardiasis
Hiatal Hernia
Inflammatory Bowel Disease
Intestinal Motility Disorders
Irritable Bowel Syndrome
Lactose Intolerance
Trichosporon Infections
Urethral Diverticula
Urticaria
VIPomas
Vocal Cord Dysfunction
Wasp Stings
Whipple Disease

WORKUP

Lab Studies

• Serum testing for specific IgE antibodies to foods
  
  
  • Specific IgE antibodies to foods can be measured by in vitro laboratory methods (eg, IgE radioallergosorbent testing), which offers advantages when dermatographism, generalized dermatitis, or a clinical history of severe anaphylactic reactions to a given food limit skin testing.
  
  
  
  • This form of testing provides information similar to prick skin tests, but it is more expensive and generally less specific.
  
  
  
  • The CAP System fluorescent-enzyme immunoassay (FEIA) (Pharmacia Diagnostics, Uppsala, Sweden) provides a more quantitative method of determining allergen-specific IgE to food allergens.
  
  
  
  • When compared with the outcome of well-controlled oral food challenges, results of the CAP system FEIA are generally similar to those of prick skin tests in predicting symptomatic food allergy.
  
  
  
  • Quantitating food-specific IgE antibodies with this automated system can help identify patients who are highly likely to have allergic reactions (>95% probability).
  
  
  
  • Published positive and negative predictive values using this system are available. These predictive values aid in making the diagnosis, thereby reducing the need for confirmatory food challenges in some patients.
  
  
  
  • Currently, the predictive values of CAP System FEIA results are limited to several major food allergens (ie, egg, milk, peanut, fish).
  
  
  

  • The predictive values developed using the CAP System FEIA are useful in predicting the likelihood of a reaction but do not predict the severity of a reaction

• Peripheral serum measurements of eosinophils or total IgE concentrations: Results from these tests support but do not confirm the diagnosis of food allergy. Likewise, normal values do not exclude diagnosis.

• Basophil histamine-release assays: These tests are mainly limited to research settings and have not been shown conclusively to provide reproducible results useful for diagnostic testing in a clinical setting.

Other Tests

• Diet diary
  
  
  • This consists of keeping a chronological record of all foods eaten and any associated adverse symptoms. It is an inexpensive endeavor that documents the frequency of symptoms and their occurrence in relationship to food ingestion. In addition, it encourages patients to focus on their diet.
  
  
  
  • This record is occasionally helpful for identifying the food implicated in an adverse reaction; however, it is not usually diagnostic, especially when symptoms are delayed or infrequent.
  
  
  
  • Occasionally, review of the diet diary reveals that the patient is not experiencing a reaction even when eating, as an ingredient in other foods, a significant amount of a food to which they were thought to be allergic.
    
• Elimination diet
  
  
  • This is used in determining the diagnosis as well as in the treatment and prevention of food allergy.
  
  
  
  • When used as a diagnostic tool, the elimination diet requires complete avoidance of suspected foods or groups of foods for a given time period (usually 7-14 d) while monitoring for an associated decrease in symptoms.
  
  
  
  • Success depends on identifying the correct food allergen and completely eliminating it in all forms from the diet. These diets are increasingly difficult to develop and follow as more foods or foods that commonly occur in the diet are eliminated.
  
  
  
  • Additional limitations of this method include potential effects of patient or physician biases, variable patient compliance, and the time-consuming nature of the endeavor.
  
  
  
  • When the elimination diet is used as treatment, identified food allergens are removed from the diet indefinitely unless evidence exists that the food allergy has been outgrown.
    
• Skin testing
  
  
  • Prick and puncture tests are the most common screening tests for food allergy and can even be performed on infants in the first few months of life. However, the reliability of the results depends on multiple factors, including use of the appropriate extracts and testing technique, accurate interpretation of the results, and avoidance of medications that might interfere with testing (eg, antihistamines).
  
  
  
  • When used in conjunction with a standard criterion of interpretation and appropriate controls (eg, histamine: positive, saline: negative), these tests provide useful and reproducible clinical information in a short period (ie, 15-20 min) with minimal expense and negligible risk to the patient.
  
  
  
  • This is a reliable method of excluding IgE-mediated food allergies. The negative predictive accuracy is greater than 95%; however, the positive predictive accuracy is generally less than 50%, which limits clinical interpretation of positive skin test results.
  
  
  
  • Positive skin test results, in addition to the suggestion of clinical reactivity based on the history, must often be confirmed by an oral food challenge unless the patient has a thoroughly convincing history of significant food allergy.
    
• Intradermal skin testing
  
  
  • The risk of inducing a systemic reaction with this type of testing is increased in comparison to the prick or puncture method; as a result, intradermal skin testing should be avoided.
  
  
  
  • In addition, the results obtained by using this method are less specific compared to those obtained by using prick or puncture testing.
    
• Tests with uncertain diagnostic value: The diagnostic value of performing the following tests is not currently supported by objective scientific evidence:
  
  
  • Results from food-specific immunoglobulin G (IgG) or IgG subclass antibody concentration testing have not been proven to be helpful with diagnosis.
  
  
  
  • Testing for food antigen-antibody complexes has no proven diagnostic value.
  
  
  
  • Performing leukocyte cytotoxic tests is not supported by objective scientific evidence.
  
  
  
  • Results from subcutaneous provocation and neutralization testing have not been proven to be helpful for diagnosis.
  
  
  
  • Kinesiology-based testing is not recommended because objective scientific evidence has indicated this type of testing does not aid in diagnosis.

Procedures

• Food challenge confirmation of food allergy
  
  
  • This includes properly conducted elimination of and subsequent oral challenge with foods suspected of causing allergic reactions based on the medical history, skin testing results, or in vitro testing results.
  
  
  
  • Of these procedures, the double-blind placebo-controlled food challenge (DBPCFC) is the most reliable method to help diagnose and confirm food allergy and other adverse food reactions because it eliminates both patient and observer bias. However, in a clinical setting where minimal bias is suspected, open food challenges may be preferable because blinding of the food is often not required.
  
  
  
  • Conduct any food challenge in a clinic or hospital setting with the personnel and equipment necessary to treat a systemic allergic reaction available at all times. Patients undergoing a food challenge should not be on beta-blocker medications or any medication that might interfere with the treatment of anaphylaxis. Obtain intravenous access in patients with history findings that indicate the potential for a systemic reaction.
  
  
  
  • If the history of the patient suggests an anaphylactic reaction is possible following food ingestion, do not perform an oral food challenge.
    
• Open food challenge
  
  
  • This test involves the patient ingesting the suspected food, prepared in its customary fashion (ie, the challenge food is not disguised in any way).
  
  
  
  • Both the patient and the observer (eg, physician, nurse) are aware of the food being ingested.
  
  
  
  • The open food challenge is best used in clinical practice when patient and physician bias is minimal.
  
  
  
  • This type of challenge is typically used when the skin test results for the suspect food are negative or if a specific food reaction is unlikely.
  
  
  
  • Whenever the results are equivocal, perform a blinded challenge.
  
  
  
  • Patients with histories of a previous reaction should never perform an open food challenge at home, even if the chance they will develop severe symptoms is remote.
    
• Single blinded food challenge
  
  
  • This challenge involves the patient ingesting the suspected food disguised in a challenge food so the patient is unaware of the contents.
  
  
  
  • This type of challenge, which is suitable for clinical practice and some research investigations, is designed to reduce patient bias during the procedure. However, subjective attitudes regarding the outcome of the challenge cannot be completely eliminated.
  
  
  
  • This test is also useful for screening patients for entry into studies in which the findings will be unequivocally confirmed by DBPCFC results.
    
• Double-blind placebo-controlled food challenge
  
  
  • DBPCFC involves ingestion of the suspected food disguised in another food so that both the patient and observer are unaware of the contents of the challenge.
  
  
  
  • This type of challenge is designed to reduce both patient and observer bias and subjective attitudes during the procedure.
  
  
  
  • Always perform this challenge in a clinic or hospital setting.
  
  
  
  • Consider this the criterion standard for diagnosing food allergy, especially in research investigations. Currently, it is the only completely objective method for determining the validity of the history of an adverse reaction to a food.
  
  
  
  • Do not perform a challenge if the patient has a clearly convincing history of a severe life-threatening anaphylactic reaction following the isolated ingestion of a specific food.

TREATMENT

Medical Care

• Education
  
  
  • Education is of paramount importance for patients with food allergies.
  
  
  
  • Patients can obtain useful resource information by contacting the Food Allergy and Anaphylaxis Network (toll-free phone number is 800-929-4040) and the International Food Information Council (phone number is 202-296-6540 and email address is foodinfo@ific.org).
  
  
  
  • Remember that appropriate restriction and complete avoidance of the relevant food allergen(s) is the only current effective therapy.
    
• Elimination of food allergen
  
  
  • Once a food allergy is diagnosed, strict elimination of the offending food allergen from the diet and avoidance of any contact with the food either by ingestion, skin contact, inhalation, or injection is necessary.
  
  
  
  • Elimination and strict avoidance is the only proven medical therapy for this allergic disease.
    
• Recognize the early signs and symptoms of an allergic reaction. Keep in mind that cutaneous, gastrointestinal, and respiratory symptoms are the most common clinical manifestations of food allergy.

Consultations

• Consultation with a nutritionist or nutrition service is invaluable in the overall management. The elimination diet can be reviewed and appropriate substitutions can be recommended. Dietary deficiencies can be anticipated and prevented.



• Consultation with a gastroenterologist is also useful in the evaluation of selected patients. For example, patients presenting with possible anatomic gastrointestinal abnormalities, eosinophilic esophagitis or gastroenteritis, failure to thrive, and malabsorption syndromes may benefit from consultation with both an allergist and a gastroenterologist.

Diet

• A properly managed well-balanced elimination diet (eg, allergen restriction) can lead to resolution of symptoms and help avoid nutritional deficiencies.



• Educate the patient and family about how to properly read food labels and identify common words used for indicating the presence of the food allergen of concern (eg, casein and whey for milk).



• With elimination diets, only exclude those foods confirmed to provoke allergic reactions.



• Review obvious and hidden sources of food allergens. Be aware of the potential for exposures by routes other than ingestion, such as skin contact, inhalation, or injection.



• Anticipate potential candidates for food allergen cross-reactivity, such as the following:
• • Eggs and chicken (less than 5%)
  
  
  
  • Cow milk and beef (10%)
  
  
  
  • Cow milk and goat milk (>90%)
  
  
  
  • Fish (>50%)
  
  
  
  • Peanuts and related legumes (less than 10%)
  
  
  
  • Soy and related legumes (less than 5%)
  
  
  
  • Wheat and other grains (25%)
  
  
  
  • Tree nuts and other nuts (>50%)
    
• Encourage avoidance of high-risk situations (eg, buffets, picnics), where accidental or inadvertent ingestion of food allergens can occur.

MEDICATION

Despite following stringent avoidance measures for clinically relevant food allergens, accidental or inadvertent ingestions occur all too often. Therefore, a concise written plan for the treatment of allergic reactions resulting from accidental exposure to the food must be available to the patient. For patients with a history of a mild reaction, such as urticaria and pruritus following the ingestion of a food allergen, treatment may be limited to an oral antihistamine. However, the potential for a more severe reaction on subsequent exposures must be taken into consideration because of the possibility of the ingestion of a larger dose than previously ingested or an unexpected or unrecognized increase in the patient’s degree of sensitivity.

If the patient has significant systemic symptoms, the treatment of choice is epinephrine administered by intramuscular injection in the lateral thigh. Examples of systemic manifestations of food allergy include generalized urticaria, laryngeal edema, lower respiratory symptoms (eg, chest tightness, dyspnea, wheezing), and hypotension. Administer epinephrine to any patient with history of a severe allergic reaction as soon as ingestion of the food allergen is discovered and the first symptoms appear.

For the medical therapy of food allergen–induced allergic reactions, the use of antianaphylactic agents, antihistamines, bronchodilators, and corticosteroids in combination with the administration of intravenous fluids and oxygen (when indicated), is suggested.

Drug Category: Adrenergic agonists

Used in the emergency management of systemic allergic reactions or anaphylaxis (eg, urticaria, angioedema, bronchospasm, cardiovascular collapse). Effects are immediate and dramatic. Appropriate use of this class of medication can be lifesaving, especially in the emergency management of anaphylaxis.

Drug Name	Epinephrine (Adrenaline, EpiPen)
Description	DOC for treating anaphylaxis. Helps decrease symptoms of anaphylaxis by increasing systemic vascular resistance, elevating diastolic pressure, producing bronchodilation, and increasing inotropic and chronotropic cardiac activity. In addition, helps reduce urticaria, angioedema, laryngeal edema, and other systemic manifestations of anaphylaxis.
Adult Dose	0.3 mL SC of 1:1000 aqueous injected (usual range is 0.2-0.5 mL) q10-15min, not to exceed 3 doses; may need to decrease dose to 0.2 mL in elderly persons or those with known cardiac conditions 0.3 mL IM of 1:1000 dilution q10-15min; IV route (1:10,000) seldom used; not to exceed 0.25 mg; given very slowly and with extreme caution 0.3-mg self-injectable devices (Epi-Pen)
Pediatric Dose	IM dosing in children based on weight or 0.01 mL/kg IM of 1:1000 dilution; not to exceed 0.3 mL IM 1:2000 dilution q10-15min0.15-mg self-injectable devices (Epi-Pen Jr)
Contraindications	Documented hypersensitivity; cardiac arrhythmias, coronary artery insufficiency, or angle-closure glaucoma; local anesthesia in areas such as fingers or toes because vasoconstriction may produce sloughing of tissue; do not use during labor (may delay second stage of labor)
Interactions	Increases toxicity of beta- and alpha-blocking agents and that of halogenated inhalational anesthetics, ie, drugs that may sensitize the heart to arrhythmias
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Dose may be decreased in elderly patients to 0.2 mL; may cause disturbing reactions such as fear, anxiety, tenseness, restlessness, throbbing headache, weakness, dizziness, pallor, respiratory difficulty, palpitation, tachycardia, tremor, and arrhythmia; use with caution in patients with cardiovascular disease, hyperthyroidism, and diabetes; properly train patients with use of self-injectable devices; advise patients to seek medical attention if using self-injectable devices to manage allergic reactions

Drug Category: Antihistamines (histamine-1 blockers)

Inhibit many responses to histamine. Histamine, via H1 receptors, causes smooth muscle contraction, increased capillary permeability, and formation of edema. During hypersensitivity reactions, histamine is one of the major potent mediators released. Blocking effects of this mediator with specific antihistamines is useful in emergency management of allergy symptoms.

Drug Name	Diphenhydramine (Benadryl, Benylin)
Description	Frequently used antihistamine for management of acute allergic symptoms. Medication has significant antimuscarinic activity and pronounced tendency to induce sedation. Approximately half of those treated with conventional doses experience some degree of somnolence.
Adult Dose	25-50 mg PO q6h 50-75 mg IV/IM q6h; IV drip may afford better control of symptoms (5 mg/kg/d); not to exceed 300 mg in 24 h
Pediatric Dose	1-2 mg/kg/dose PO q6h 1-2 mg/kg/dose IV/IM q6h; IV drip may afford better control of symptoms (5 mg/kg/d)
Contraindications	Documented hypersensitivity; MAO inhibitors; glaucoma, gastrointestinal obstruction, hyperthyroidism, hypertension, and cardiovascular disease; may limit use in elderly patients
Interactions	Potentiates effect of CNS depressants; due to alcohol content, do not give syrup dosage form to patient taking medications that can cause disulfiramlike reactions
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Adverse anticholinergic effects and drowsiness; large doses may depress respiration; use can potentially worsen glaucoma, gastrointestinal or urinary obstruction, hyperthyroidism, and hypertension; dizziness, paradoxical excitement, gastritis, and blood dyscrasias; caution with performing certain motor skills (eg, operating heavy machinery, driving a motor vehicle)

Drug Category: Antihistamines (histamine-2 blockers)

Drug Name	Ranitidine (Zantac)
Description	H2-receptor antagonists competitively inhibit the interaction of histamine with H2 receptors. These are highly selective and have little or no effect on H1 receptors. H2-receptor antagonists are primarily used for the management of active duodenal or benign gastric ulcer disease. They are also used in the healing of duodenal or benign gastric ulcers.
Adult Dose	150 mg PO q8-12h 50 mg IV q6-8h
Pediatric Dose	Safety not established
Contraindications	Documented hypersensitivity
Interactions	May decrease effects of ketoconazole and itraconazole; may alter serum levels of ferrous sulfate, diazepam, nondepolarizing muscle relaxants, and oxaprozin
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Caution in renal or liver impairment and nursing mothers; if changes in renal function occur during therapy, consider adjusting dose or discontinuing treatment

Drug Name	Cimetidine (Tagamet)
Description	H2-receptor antagonists competitively inhibit interaction of histamine with H2 receptors. These are highly selective and have little or no effect on H1 receptors. Used in hypersecretory conditions, intractable duodenal ulcers, and for prevention of upper gastrointestinal bleeding.
Adult Dose	300 mg PO q6-8h 300 mg IV q6-8h
Pediatric Dose	less than 16 years: Not recommended >16 years: 20-40 mg/kg/d PO/IV
Contraindications	Documented hypersensitivity
Interactions	Can increase blood levels of theophylline, warfarin, TCAs, triamterene, phenytoin, quinidine, propranolol, metronidazole, procainamide, and lidocaine
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Elderly patients may experience confusional states; may cause impotence and gynecomastia in young males; may increase levels of many drugs; adjust dose or discontinue treatment if changes in renal function occur

Drug Name	Famotidine (Pepcid)
Description	H2-receptor antagonists competitively inhibit the interaction of histamine with H2 receptors. Highly selective and have little or no effect on H1 receptors. Used for active duodenal ulcers, maintenance of healed duodenal ulcers, and active benign gastric ulcers. Also used for gastroesophageal reflux disease and associated esophagitis. Individualize and adjust dose based on response.
Adult Dose	20-40 mg PO/IV q12h
Pediatric Dose	less than 1 years: Not recommended 1-16 years: 0.5 mg/kg/d divided doses PO/IV; not to exceed 40 mg/d
Contraindications	Documented hypersensitivity
Interactions	May decrease effects of ketoconazole and itraconazole
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Reduce dose or prolong dosing interval with severe renal insufficiency (CrCl less than 10 mL/min); not recommended for nursing mothers; adverse reactions include headache, dizziness, constipation, diarrhea, somnolence, seizures, palpitations, depression, and injection site reactions

Drug Category: Bronchodilators

Patients experiencing significant adverse respiratory symptoms as part of their food-induced allergic reaction must be managed aggressively with nebulized bronchodilators. Nebulized adrenergic agonists or bronchodilators are usually administered for treatment of bronchospasm. Supplemental oxygen can also be administered with nebulizations. In selected cases, parenteral agents may be employed to achieve sufficient bronchodilation.

Drug Name	Albuterol (Proventil, Ventolin)
Description	Common bronchodilator used in clinical medicine.
Adult Dose	2.5-5 mg (0.5 mL of 5% solution diluted to a final volume of 3 mL with 0.9% saline) nebulized over 5-15 min q20min, not to exceed 6 doses; also available in unit dose vials (3 mL of 0.083% solution) for nebulization
Pediatric Dose	Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Beta-adrenergic blockers antagonize effects; inhaled ipratropium may increase duration of bronchodilatation by albuterol; cardiovascular effects may increase with MAOIs, inhaled anesthetics, TCAs, and sympathomimetic agents
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in hyperthyroidism, diabetes mellitus, and cardiovascular disorders; avoid excessive use with cardiac disease, arrhythmia, hypertension, hyperthyroidism, seizure disorders, labor, and delivery; not recommended for nursing mothers

Drug Name	Metaproterenol (Alupent, Dey-Dose, Prometa)
Description	Beta2-adrenergic agonist that relaxes bronchial smooth muscle with little effect on heart rate.
Adult Dose	0.3 mL of 5% solution diluted in 2.5 mL of 0.45% or 0.9% normal saline nebulized over 5-15 min q4h
Pediatric Dose	0.1-0.2 mL of 5% solution diluted in 3 mL of 0.45% or 0.9% normal saline nebulized over 5-15 min q4h
Contraindications	Documented hypersensitivity; arrhythmia associated with tachycardia
Interactions	Decreases effect of beta-receptor blockers; increases toxicity of MAOIs, TCAs, and sympathomimetics
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in hypertension, cardiovascular disease, congestive heart failure, hyperthyroidism, diabetes, and seizures; not recommended for nursing mothers; adverse reactions include tachycardia, headache, nervousness, dizziness, tremor, gastrointestinal upset, hypertension, paradoxical bronchospasm, and cough

Drug Name	Theophylline (Aquaphyllin, Aminophyllin)
Description	Potentiates exogenous catecholamines and stimulates endogenous catecholamine release and diaphragmatic muscular relaxation, which, in turn, stimulates bronchodilation.
Adult Dose	5-6 mg/kg IV loading dose in 20 mL D5W over 10-15 min, followed by a maintenance dose of 0.5-1 mg/kg/h
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; uncontrolled arrhythmias, peptic ulcers, hyperthyroidism, and uncontrolled seizure disorders
Interactions	Aminoglutethimide, barbiturates, carbamazepine, ketoconazole, loop diuretics, charcoal, hydantoins, phenobarbital, phenytoin, rifampin, isoniazid, and sympathomimetics may decrease effects; effects may increase with allopurinol, beta-blockers, ciprofloxacin, corticosteroids, disulfiram, quinolones, thyroid hormones, ephedrine, carbamazepine, cimetidine, erythromycin, macrolides, propranolol, and interferon
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in peptic ulcer, hypertension, tachyarrhythmias, hyperthyroidism, and compromised cardiac function; do not inject IV solution >25 mg/min; patients with pulmonary edema or liver dysfunction are at greater risk of toxicity because of reduced drug clearance

Drug Category: Corticosteroids

Ameliorate delayed effects of anaphylactoid reactions and may limit biphasic anaphylaxis. In severe cases of serum sickness, parenteral steroids may be beneficial to reduce inflammatory effects of this immune complex–mediated disease.

Drug Name	Methylprednisolone (Medrol, Adlone, Solu-Medrol)
Description	For treatment of inflammatory and allergic reactions. By reversing increased capillary permeability and suppressing PMN activity, may decrease inflammation.
Adult Dose	60-80 mg IV for 1 dose; then q6h
Pediatric Dose	1-2 mg/kg/dose IV q6h; not to exceed 60-80 mg
Contraindications	Documented hypersensitivity; viral, fungal, or tubercular infections
Interactions	Coadministration with digoxin may increase digitalis toxicity secondary to hypokalemia; estrogens may increase levels; phenobarbital, phenytoin, and rifampin may decrease levels (adjust dose); monitor patients for hypokalemia when taking medication concurrently with diuretics
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Hyperglycemia, edema, osteonecrosis, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, growth suppression, myopathy, and infections are possible complications of glucocorticoid use

Drug Name	Hydrocortisone (Cortef)
Description	Has mineralocorticoid and glucocorticoid effects. Useful in management of inflammation caused by immune response.
Adult Dose	100-200 mg IV q6-8h
Pediatric Dose	Not to exceed 5-10 mg/kg IV q6-8h
Contraindications	Documented hypersensitivity; viral, fungal, or tubercular infections
Interactions	Corticosteroid clearance may decrease with estrogens; may increase digitalis toxicity secondary to hypokalemia
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in hyperthyroidism, osteoporosis, peptic ulcer, cirrhosis, nonspecific ulcerative colitis, diabetes, and myasthenia gravis

Drug Name	Prednisone (Deltasone, Meticorten, Sterapred)
Description	Immunosuppressant for treatment of autoimmune disorders; may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.
Adult Dose	20-40 mg PO qd with quick taper
Pediatric Dose	1-2 mg/kg/d PO with quick taper; not to exceed 20-40 mg
Contraindications	Documented hypersensitivity; viral infection, peptic ulcer disease, hepatic dysfunction, connective tissue infections, and fungal or tubercular skin infections; GI disease
Interactions	Coadministration with estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use

FOLLOW-UP

Deterrence/Prevention

• Emergency plan
  
  
  • Provide a written emergency treatment plan for the patient. Have copies of this plan available in appropriate places (eg, daycare, schools, work locations, college dormitory advisors).
  
  
  
  • Patients with food allergies should be advised to obtain and wear Medic Alert tags or bracelets indicating their specific food allergies.
  
  
  
  • Ensure that the patient has an emergency contact number available (eg, 911, their physician's office phone number, or a local emergency department) that can be used in the event of a major food-induced allergic reaction.
  
  
  
  • Anticipatory guidance measures cannot be overemphasized; for example, educate the patient about potential sources of accidental or inadvertent exposure to relevant food allergens (eg, daycare, school, travel, picnics, dining out).
    
• Emergency medications
  
  
  • Ensure that the patient has self-injectable epinephrine readily available at all times. Also ensure that the patient receives proper training regarding when and how to use the device. An antihistamine (syrup or chewable tablet) should also be available. Patients with food allergies and asthma should always have access to a rapid-acting bronchodilator.
  
  
  
  • Self-injectable epinephrine is typically available by prescription (ie, Epi-Pen, Epi-Pen Jr, Twinject). These devices should be stored properly (avoiding extremes of temperature) and replaced before the expiration date.
  
  
  
  • Injectable epinephrine is the drug of choice for the initial management of a food-induced anaphylactic reaction.

Prognosis

• Developing intolerance
  
  
  • In general, most infants and young children outgrow or become clinically tolerant of their food hypersensitivities.
  
  
  
  • Well-controlled prospective investigations of food allergy in infants and children demonstrate that by following proper elimination diets, 85% of confirmed symptoms resolve by 3 years of age.
  
  
  
  • Adults with food allergy can also lose their clinical allergic reactions to foods after implementation of appropriate food elimination diets.
  
  
  
  • Approximately one third of all children and adults lose their clinical reactivity to specific food allergens after 1-2 years of appropriate food allergen elimination therapy. Patients with allergies to peanuts, tree nuts, fish, and shellfish rarely lose their clinical reactivity.
    
• Avoidance of allergen
  
  
  • How strictly the patient complies with the allergen avoidance diet appears to be directly associated with the ultimate clinical outcome (ie, development of oral tolerance).
  
  
  
  • Patients with allergic reactions to peanuts, tree nuts, shellfish, and fish rarely lose their clinical reactivity.
    
• Breastfeeding
  
  
  • While exclusive breastfeeding is frequently promoted as a means of preventing food allergy and atopic disease in general, considerable controversy remains regarding the effectiveness of this practice.
  
  
  
  • Some investigations suggest that lactating mothers should eliminate highly allergenic foods (eg, peanuts, tree nuts, shellfish) that may induce life-long allergic sensitivity in their infants.
  
  
  
  • Further studies are needed to clarify the role of early elimination diets and breastfeeding in the prevention of food allergy.

Patient Education

• Preparation
  
  
  • Always carry an epinephrine self-injectable device that has been properly stored and is current (ie, not expired).
  
  
  
  • Have an H1-blocker medication (again, properly stored and not expired) in a syrup or chewable tablet form available.
    
• Avoidance of allergen
  
  
  • Complete avoidance of the offending food allergen is the best strategic approach and the only proven therapy once the diagnosis of food hypersensitivity is established; therefore, these patients should be properly taught to recognize relevant food allergens that must be eliminated from their diet.
  • Instruct the patient about the proper reading of food labels and the need to inquire about food ingredients when dining out.
  
  
  
  • Encourage the patient to become familiar with recognizing different words that signify particular food allergens (eg, for cow milk, terms such as casein, whey, beta-lactoglobulin, alpha-lactalbumin).
  
  
  
  • If the patient is in doubt about a food or food ingredient, suggest avoidance of the food in question.
    
• Support groups
  
  
  • Inform patients with food allergies how to identify and use support groups.
  
  
  
  • One such organization is the Food Allergy and Anaphylaxis Network (10400 Eaton Place, Suite 107, Fairfax, VA, 22030-2208 USA; fax: 703-691-2713; phone: 703-691-3179 or 800-929-4040; email: faan@foodallergy.org).
  
  
  
  • Another such organization is the International Food Information Council (1100 Connecticut Avenue NW, Suite 43, Washington, DC, 20036 USA; fax: 202-296-6547; phone: 202-296-6540; email: foodinfo@ific.org).
    
• Early detection
  
  
  • Educate patients regarding recognition of the early signs and symptoms of a food-induced allergic reaction, and provide them with a written management plan for successfully dealing with these reactions.
  
  
  
  • Write a specific list of clinical signs and symptoms to look for if a reaction may be occurring, and include a clear management plan. An excellent example of such a plan is available on The Food Allergy and Anaphylaxis Network Web site.
  
  
  
  • Demonstrate to the patient and family how to actually administer medications, especially injectable epinephrine, in the event of an allergic reaction. To accomplish this, use demonstration trainer devices in the clinic setting. Reinforce that if injectable epinephrine is administered, the patient must be immediately evaluated in a medical setting.
    
• For excellent patient education resources, visit eMedicine's Allergy Center and Allergic Reaction and Anaphylactic Shock Center. Also, see eMedicine's patient education articles Food Allergy and Severe Allergic Reaction (Anaphylactic Shock).

MISCELLANEOUS

Medical/Legal Pitfalls

• When performing oral food challenges, be prepared to recognize and treat adverse clinical symptoms immediately. Appropriately trained personnel and the necessary equipment for the treatment of anaphylactic shock must be available prior to and throughout the entire oral food challenge and observation period because of the risk of triggering an allergic reaction.



• Do not perform an oral food challenge if the patient has a clear and convincing history of a severe life-threatening anaphylactic reaction following the isolated ingestion of a specific food. This is an absolute contraindication.



• Patients should never perform an open food challenge at home if even a remote chance exists that the patient will develop severe symptoms.



• Confirm negative results from a DBPCFC using an open feeding (open food challenge) of the food in question before giving final advice on dietary restrictions.



• If the patient has a history of severe allergic reactions following the ingestion of food allergens, give specific advice in the form of a written emergency treatment plan. In addition, educate the patient on how to administer emergency medications (eg, injectable epinephrine, antihistamines) in the event of a severe life-threatening allergic reaction. Encourage the patient (when appropriate) or a caretaker to carry these medications with them at all times in case they are needed to manage symptoms.

Special Concerns

• Diagnosis
  
  
  • Because specific laboratory tests for some food hypersensitivities are not available, diagnosing non–IgE-mediated food allergies (eg, cow milk–induced and soy-induced enterocolitis syndromes, allergic eosinophilic gastroenteritis) is more difficult than diagnosing IgE-mediated food allergies.
  
  
  
  • In cases of allergic eosinophilic gastroenteritis, a biopsy may need to be performed. Elimination diets with gradual reintroduction of foods and supervised oral food challenges are often needed to help identify the causative foods.
  
  
  
  • For food protein–induced enterocolitis syndrome, perform a food challenge with 0.15–0.30 grams of protein per kilogram of body weight of the implicated protein and observe the patient for several hours. Positive reactions (eg, profuse vomiting and diarrhea) are typically accompanied by a rise in the absolute neutrophil count of more than 3500 cells/mm³. Because of the potential for shock, these challenges are best performed in the hospital setting.
  
  
  
  • When the history of an allergic reaction to a food suggests that the onset of symptoms is delayed by hours or days following ingestion, adjust the timing and monitoring of the challenge to correspond to these characteristics.
  
  
  
  • The successful administration of oral food challenges to young children requires a great deal of preparation, patience, and creativity. Young children may refuse to ingest the challenged food. Prior planning with the family is important to choose proper vehicles (eg, juice, cereal, solid food) for disguising the challenged substance.
    
• Vaccines
  
  
  • Recent scientific data support the routine 1-dose administration of the measles-mumps-rubella vaccine to all patients with egg allergy, even those with severe anaphylactic reactions following egg ingestion. In the child with a history of a previous reaction to the measles-mumps-rubella vaccine, consider the possibility of allergy to gelatin or neomycin.
  
  
  
  • If the patient has a clinical history of egg allergy and has experienced systemic reactions (eg, anaphylaxis) following the ingestion of egg, the administration of the influenza vaccine requires special diagnostic consideration. Test the patient's skin with diluted preparations of the influenza vaccine (ie, puncture skin testing and, if needed, intradermal skin testing). If skin test results with the vaccine are positive, the vaccine can be safely given in a graded, multidose scheme. If results are negative, the vaccine may be administered in the routine 1-dose manner.