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).
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.
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%).
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.
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.
No predilection is known.
No predilection is known.
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%.
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.
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.
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.
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.
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.
Following the ingestion of food, severe anaphylactic reactions (ie, systemic allergic reactions), including death, can occur.
Symptoms may include the following:
Angioedema (eg, laryngeal edema)
Ocular injection, ocular pruritus, conjunctival edema, periocular swelling
Nasal congestion, nasal pruritus, rhinorrhea, and sneezing
A feeling of impending doom
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)
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.
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.