Practice Essentials

Food allergies are immunologically mediated adverse reactions to foods. 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.

Signs and symptoms

Signs and symptoms of food-induced anaphylaxis can include the following:

Oropharyngeal pruritus

Angioedema (eg, laryngeal edema)

Stridor

Dysphonia

Cough

Dyspnea

Wheezing

Nausea

Vomiting

Diarrhea

Flushing

Urticaria

Angioedema

Ocular injection, ocular pruritus, conjunctival edema, periocular swelling

Nasal congestion, nasal pruritus, rhinorrhea, and sneezing

Abdominal pain
 Feeling of impending doom

Cardiovascular collapse

Necessary elements of a thorough medical history include the following:

Complete list of all foods suspected of causing symptoms

Manner in which the food was prepared (cooked, raw, added ingredients)

Minimum quantity of food exposure required to cause the symptoms

Reproducibility of symptoms on exposure to the food

Personal or family history of other allergic disease

Factors that can potentiate a food-allergic reaction (eg, exercise, [1] nonsteroidal anti-
inflammatory drugs [NSAIDs], or alcohol)

In addition, obtain a thorough description of each reaction, including the following:

Route of exposure (ingestion, skin contact, inhalation) and dose

Timing of symptom onset in relation to food exposure

All observed symptoms and each ones severity

Duration of the reaction

Treatment provided and clinical response to treatment

Most recent reaction

Physical examination findings are most useful for the following:

Assessing nutritional status, growth parameters, and signs of other allergic disease

Helping to rule out other conditions that may mimic food allergy

See Clinical Presentation for more detail.

See All About Allergies: Be Ready for Spring, a Critical Images slideshow, to help identify a
variety of allergens and symptoms.

Diagnosis
Laboratory studies that may be helpful include the following:

Specific immunoglobulin E (IgE) antibody testing: Positive results primarily denote

sensitization and may not confirm clinical allergy; specific laboratory tests for some food
hypersensitivities are not available

Basophil histamine-release assays: These are limited primarily to research settings

Skin testing includes the following approaches:

Prick testing: This is the most common screening test for food allergy; negative
predictive accuracy exceeds positive predictive accuracy (>90% vs < 50%)

Intradermal testing: Generally avoided, because of the risk of inducing a systemic

reaction

Patch testing: Appears promising, but additional studies are needed and it is not
recommended for routine practice

Diet-related diagnostic measures may be helpful, as follows:

Diet diary

Elimination diet (may be used for diagnostic as well as therapeutic purposes)

Food challenge confirmation of food allergy (may be open; single-blind; or double-blind,

placebo-controlled)

See Workup for more detail.

Management

There are currently no curative therapies for food allergy. The only proven treatment is strict
dietary elimination of the offending food allergen. A properly managed, well-balanced
elimination diet includes the following elements:

Education of patients and families regarding how to read food labels properly and
identify common words used for indicating the presence of the food allergen of concern

Avoidance of cross-contact (eg, through shared utensils or fryers) of allergens with

otherwise safe foods during meal preparation

Elimination of only those foods that are confirmed as provoking allergic reactions; both
obvious and hidden sources of food allergens (eg, medications and cosmetics) must be
considered
 Consideration of potential exposures by route other than ingestion (eg, skin contact or
inhalation)

Anticipation of potential candidates for food allergen cross-reactivity (eg, peanut and
lupine or cow milk with sheep milk) [2]

Avoidance of high-risk situations where accidental or inadvertent ingestion of food

allergens can occur (eg, buffets or picnics)

Adherence to avoidance measures notwithstanding, accidental or inadvertent ingestions may

occur and lead to a reaction. Strategies for dealing with such a reaction include the following:

Creation of a concise written emergency management plan (see www.foodallergy.org),

copies of which should be available in appropriate places (eg, daycare, schools, work
locations, and college dormitory advisors)

Use of medical identification jewelry indicating food allergies

Ensuring that the patient has an emergency contact number available

Provision of anticipatory guidance measures (eg, educating the patient about potential
sources of accidental exposure)

Emergency medications include the following:

Injectable epinephrine: This is the drug of choice for initial management of a food-
induced anaphylactic reaction; the patient should have self-injectable epinephrine readily
available at all times and should be properly trained in its use

Antihistamines may be used for the treatment of mild symptoms

Bronchodilators may be used but should not be depended upon for anaphylaxis;
epinephrine should be given

Histamine-2 blockers as adjunctive therapy

Corticosteroids as adjunctive therapy

Intravenous fluids for hypotension

Glucagon for refractory anaphylaxis

In severe anaphylaxis, ventilatory and circulatory support may be needed.

Oral or sublingual immunotherapy appears to be a promising therapeutic option for the future. [3,
4]

See Treatment and Medication for more detail.

Background
Food allergies are immunologically mediated adverse reactions to foods. Such allergies can
result in disorders with an acute onset of symptoms following ingestion of the triggering food
allergen (eg, anaphylaxis), as well as in chronic disorders (eg, atopic dermatitis, eosinophilic
esophagitis). Symptoms observed in a food-induced anaphylactic reaction may involve the skin,
gastrointestinal tract, and respiratory tract. (See Pathophysiology, Etiology, and Presentation.) [5]

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 (medically supervised, gradual test feedings) . Sesame appears to be an emerging
allergen. (See Etiology and Workup.)

Investigations of near-fatal or fatal anaphylactic reactions following food ingestion reveal that
most are caused by peanuts, tree nuts, and shellfish, although milk has been increasingly
reported. (See Workup.) [6]

Adverse reactions to food that are not immune mediated are not considered to be food allergies.
An example is lactose intolerance, which is caused by a deficiency of lactase. Adverse reactions
to foods can also occur from toxic (eg, bacterial food poisoning) or pharmacologic (eg, caffeine)
effects.

Pathophysiology
Although anaphylaxis can occur without skin symptoms, cutaneous reactions 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

Controversy surrounds the role of food allergy in the pathogenesis of atopic dermatitis. [7] Studies
show that among patients with moderate chronic atopic dermatitis, 35-40% have IgE-mediated
food allergy. [8, 9] Food-specific IgE-mediated and cellular mechanisms appear responsible for
chronic eczematous inflammation.

Removal of a specific food allergen may lead to reduction or resolution of clinical symptoms in
affected patients; reintroduction of the food may then exacerbate the atopic dermatitis if it is
food-responsive. [10, 11] 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. [12]

In a study of 619 exclusively breastfed infants, those with atopic dermatitis were significantly
more likely to be sensitized to foods. [13, 14] In addition, a strong association between the severity
of the dermatitis and sensitization was observed, and positive associations between atopic
dermatitis and specific foods (egg, cows milk, and peanut) were found.

In addition to skin-prick testing against cow's milk, egg, cod fish, wheat, sesame, and peanut,
infants in the study were screened for filaggrin loss-of-function (FLG) gene mutations. [14] FLG
mutations were significantly associated with incidence of atopic dermatitis and higher median
transepidermal water loss relative to dermatitis severity. Although children with atopic dermatitis
were significantly more likely to be sensitized to foods, this effect was not related to FLG
mutation inheritance.

Celiac disease

Celiac disease is the result of an immune response to gluten proteins in grain.

Dermatitis herpetiformis

This is a form of non-IgE cell-mediated hypersensitivity related to celiac disease. It is a blistering

skin disorder that manifests clinically with a chronic and intensely pruritic rash with a
symmetrical distribution. 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. [15]

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, peach or hazelnut.
Mixed IgE/non-IgE gastrointestinal food allergy (eosinophilic esophagitis and
gastroenteritis)

Symptoms vary according to location of the eosinophilia. Typical symptoms include postprandial
nausea, abdominal pain, and a sensation of early satiety. Eosinophilic esophagitis may manifest
as reflux symptoms and dysphagia; food impaction can occur as well. Children may experience
weight loss or failure to thrive. [16]

A complete blood count (CBC) 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 affected segment of the gut.
While a dense eosinophil infiltrate may be seen anywhere from the lower esophagus through the
large bowel, involvement is patchy and variable.

Eosinophilic esophagitis is characterized by symptoms related to esophageal dysfunction, such as

dysphagia and pain, and histologically by eosinophil-predominant inflammation. Pathologically,
1 or more biopsy specimens must show a peak of 15 or more eosinophils per high power field.
Alternative explanations (eg, reflux) for symptoms/histopathologic abnormalities should be
excluded.

An elemental (no potential allergens) or oligoantigenic diet (a diet that removes common
allergenic foods) and trials of food elimination may be required to determine the role of foods in
a patient's condition.

In addition to diet therapy (or in place of diet therapy), treatment with anti-inflammatory
medications (eg, corticosteroids) may be needed. Eosinophilic esophagitis appears to be a
chronic disease and fibrosis and stricture formation could occur. Updated diagnostic and
treatment approaches have been proposed. [17]

NonIgE-mediated gastrointestinal food allergy

Food proteininduced enterocolitis syndrome (FPIES) typically manifests in the first few months
of life with severe projectile vomiting, diarrhea, and failure to thrive. [18] Cow milk and soy
protein formulas are usually responsible for these reactions. However, solid foods may also
trigger these reactions, especially rice and oats. [19]

When the allergen is removed from the diet, symptoms resolve. Reexposure prior to resolution
results in a delayed (2h) onset of vomiting, lethargy, increase in the peripheral blood
polymorphonuclear leukocyte count, and, later, diarrhea. Hypotension and methemoglobinemia
may occur.

Infants with FPIES who are chronically ingesting the allergen typically appear lethargic, wasted,
and dehydrated. The presentation may mimic sepsis. An oral food challenge may establish the
diagnosis but is not always needed if the history is clear. No other definitive diagnostic tests are
available.
Breastfed infants may have mucus and blood in their stool, attributed to food allergens ingested
by the mother, primarily cow milk. This allergic proctocolitis does not typically lead to anemia
and is not associated with vomiting or poor growth. Maternal exclusion of the allergen resolves
the bleeding. Eosinophilic inflammation of the rectum is noted if a biopsy is performed. [20]
Additional causes of bleeding (eg, infection, fissures) should be considered.

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

Although wheezing can occur during a food-allergic reaction, foods do not appear to be a
common trigger for chronic asthma. [21, 22, 23]

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.

Etiology
Food allergies are primarily the result of immune responses to food proteins. (Allergic reactions
to non-protein food additives are uncommon. [22] ) Normally, noninflammatory immune responses
develop to ingested foods in a process called oral tolerance. [24, 25] For reasons that remain unclear,
but likely include environmental and genetic factors, tolerance may be abrogated, leading to
adverse immune responses.

While sensitization (eg, development of an immunoglobulin E [IgE] immune response) to an

allergen has been primarily assumed to occur from ingestion, this may not always be the case.
For example, oral allergy syndrome (pollen-food related syndrome) describes an allergic
response to specific raw fruits or vegetables that share homologous proteins with pollens; the
initial route of sensitization is respiratory exposure to pollen proteins rather than oral exposure to
food proteins. The skin may be another potential route of sensitization. [26]

IgE antibody-mediated responses

IgE antibodymediated responses are the most widely recognized form of food allergy and
account for acute reactions. Patients with atopy produce IgE antibodies to specific epitopes
(areas of the protein) of one or more food allergens. These antibodies bind to high-affinity IgE
receptors on circulating basophils and tissue mast cells present throughout the body, including in
the skin, gastrointestinal tract, and respiratory tract.

Subsequent allergen exposure binds and cross links IgE antibodies on the cell surface, resulting
in receptor activation and intracellular signaling that initiates the release of inflammatory
mediators (eg, histamine) and synthesis of additional factors (eg, chemotactic factors, cytokines)
that promote allergic inflammation. 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 acute allergic reactions to
food.

Cell-mediated responses

Cell-mediated responses to food allergens may also mediate allergic responses, particularly in
disorders with delayed or chronic symptoms. For example, food proteininduced enterocolitis
syndrome (FPIES), a gastrointestinal food allergy, appears to be mediated by T-cell elaboration
of the cytokine tumor necrosis factor (TNF)-alpha. [27] Persons with atopic dermatitis that flares
with ingestion of milk have been noted to have T cells that, in vitro, express the homing receptor
cutaneous lymphocyte antigen, which is thought to home the cell to the skin and mediate the
response. [28] Celiac disease is the result of an immune response to gluten proteins in grains.

Characteristics of food allergens

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. [2] Delayed allergic reactions to meat proteins have been
attributed to reactions to carbohydrate moieties. [29]

Risk factors

Risk factors or associations 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 epinephrine to treat the allergic reaction.
[30, 6]
Teenagers and young adults appear to be overrepresented in registries of food allergy
fatalities and present a special risk group.
Epidemiology
General surveys report that as many as 25-30% of households consider at least 1 family member
to have a food allergy. [31, 32] However, this high rate is not supported by controlled studies in
which oral food challenges are used to confirm patient histories.

Comprehensive studies that include oral food challenges are few in number. Considering allergy
to milk, egg, peanut, and seafood in a meta-analysis of 6 international studies using oral food
challenges, estimated rates of 1-10.8% were obtained. [33]

In a meta-analysis including allergy to fruits and vegetables (excluding peanut), only 6

international studies included oral food challenges, and estimates of allergy varied widely from
0.1-4.3% for fruits and tree nuts to 0.1-1.4% for vegetables to under 1% for wheat, soy, and
sesame. [34]

Sex- and age-related demographics

Among children, males appear to be more affected; among adults, females are more frequently
affected. [35] The prevalence of food allergies has been estimated to be up to 8% in infants and
children and 3.7 % in adults. [36]

However, variations in prevalence have been reported according to method used (self report,
testing, physician evaluation), geographic region, and foods included in the assessment. [37]

Studies in the United States and the United Kingdom indicate a rise in peanut allergy among
young children in the past decade. [35, 38] One study showed an increase of peanut allergy in
children from 0.4% in 1997 to 0.8% in 2002. [35] Studies from Canada and the United Kingdom
indicate allergy rates to peanut of over 1% in children. [39, 40]

A report from the US Centers for Disease Control and Prevention (CDC) indicated that among
children aged 0-17 years, the prevalence of food allergies increased from 3.4% in 1997-1999 to
5.1% in 2009-2011, a 50% rise. [41]

Based on available studies, estimations of the rate of food allergies in children have been
summarized as follows for common food allergens [36] :

Cow milk - 2.5%

Eggs - 1.3%

Peanuts - 0.8%

Wheat - 0.4%

Soy - 0.4%
Prognosis
In general, most infants and young children outgrow or become clinically tolerant of their food
hypersensitivities. Specifically, most "outgrow" allergies to milk, egg, soy and wheat. Allergies
to peanut, tree nuts, fish, and shellfish are more persistent. [42]

Population-based studies generally show that 85% of young children outgrow their allergy to
milk or egg by age 3-5 years. [42] However, studies reported from a referral center showed more
persistence of egg, milk, and soy allergies, with only about 50% of patients resolving these
allergies by age 8-12 years. [43, 44, 45] Children continued to lose their allergy into adolescent years.

About 20% of infants and young children experience resolution of their peanut allergy by the
time they reach school age.

Children with non-IgEmediated food allergies, such as proctocolitis and enterocolitis, typically
resolve their food allergy in the first years of life. [46] Allergic eosinophilic esophagitis appears to
be a persistent disorder. [47]

Morbidity and mortality

Severe anaphylactic reactions, including death, can occur following the ingestion of food. [30, 6]
Fatalities result from severe laryngeal edema, irreversible bronchospasm, refractory hypotension,
or a combination thereof.

Peanuts, tree nuts, fish, and shellfish are the foods most often implicated in severe food-induced
anaphylactic reactions, although anaphylactic reactions to a wide variety of foods have been
reported. Fatalities caused by reactions to milk have increasingly been noted. [6]

Patient Education
Preparation

Patients should always carry a self-injectable device with epinephrine that has been properly
stored and is current (ie, not expired). Ensure that the patient receives proper training regarding
when and how to use the injection device. Patients should also have an H1-blocker medication
(again, properly stored and not expired) in a syrup or chewable tablet form available. In addition,
patients should be instructed to obtain immediate medical assistance (eg, call 911) in the event of
anaphylaxis.

Caregivers of children should be instructed on identification and treatment of allergic and

anaphylactic reactions.

Avoidance of allergens
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, patients
with food allergies should be 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. If the patient is in doubt about a food or food ingredient, suggest
avoidance of the food in question. Educate patients about the potential for food allergens to be
present in medications and cosmetics.

Support groups

Inform patients with food allergies how to identify and use support groups. One such
organization is the Food Allergy Research and Education group.

Early detection and treatment

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 Research and Education 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 patient education information, see the Allergies Center, as well as Food Allergy and Severe
Allergic Reaction (Anaphylactic Shock).