Food
Allergy Symptoms and Causes
By Dale Ames Kline, MS, RD, CNSD
Today’s Dietitian
Vol. 7 No. 8 P. 10
Allergies are a “trendy” condition today.
People suspect that any discomfort or symptoms indicate that their
bodies are reacting to outside influences, not malfunctioning internally.
Foods are right up there with pollen, mold, and pet dander as suspected
allergens, and an already diet-obsessive populace conjures up new
allergies on a regular basis.
True food allergies are not as common as popularly
thought. There is much debate over the incidence level, the types
of adverse reactions actually caused by sensitivities, diagnostic
methods, and treatment.
Part of the problem is terminology. Both immunologically
and nonimmunologically triggered reactions to food are called food
sensitivities, but both are not true allergies.
A food allergy is an immunologically triggered reaction
to a food component or additive, with clinical symptoms appearing
immediately or over a period of hours or days. Allergy usually involves
the antibody immunoglobulin E (IgE) binding to the allergen.
Food intolerances are another category of food sensitivities,
which are a nonimmunological physiologic response to food that can
be triggered by enzymatic disorders, food additives or contaminants,
or pharmacological agents in food.
Separating fact from fiction becomes difficult when
a patient believes the cause of his or her symptoms is food and
shows symptoms when exposed to that food. We should regard such
reactions skeptically, however, when a double-blind challenge does
not link the reaction to the food and should consider that additives
found in food, rather than the foods themselves, may be to blame.
However, foods are usually the cause of an adverse
food reaction.1 Chart 1 shows the differences between immunologic
and nonimmunologic reactions to food.
The Allergic Reaction
A true food allergy is an immunologic reaction, triggered by a digested
food antigen (usually a protein or peptide) reaching the circulatory
system. The “foreign” food antigen sets off an immune
reaction in tissues or organs mediated by IgE, mast cells and inflammatory
mediators released from the mast cells, and other granulocytes.
This is the classic food allergy and is known as Type I hypersensitivity.
The mediators then interact with end organs, resulting
in clinically observable symptoms. Mast cells and basophils are
involved in the allergic reaction. Mast cells are found below the
skin surface and below mucous surfaces in the eyes, nose, mouth,
respiratory tract, and intestine, while basophils are found in the
bloodstream. Sensitized IgE binds to the mast cells, which attach
to the antigen.
Immune cells that can recognize foreign antigens
are macrophages, dendritic cells, or B cells. The allergic reaction
starts when immune cells bind to the antigen, then “present”
the antigen to T cells, which is why these cells are also called
antigen-presenting cells (APCs). The T cells then bind the antigen
fragment to determine which specific cells and cytokines need to
be produced, thereby determining the direction of the immune response.
In the case of a Type I hypersensitivity reaction,
the T cells produce interleukin-2 (IL-2), which stimulates the production
of B cells and T helper 2 (Th2) cells. The Th2 cells then produce
IL-4, signaling the B cells to produce IgE antibodies. IgE antibodies
have an affinity for mast cell receptors, binding to them; then
they circulate in the body together.
In contrast, had the T cells signaled the body to
produce Th1 cells instead of Th2 cells, the B cells would get a
signal to produce immunoglobulin G (IgG) instead of IgE, so no allergic
reaction would occur.
When the food antigen enters the body, it binds
to the IgE, which is bound to mast cells. When a food antigen binds
to two adjacent IgE antibodies, it is known as cross-linking, triggering
the release of granules inside the mast cells into the surrounding
fluids.
Contained in the granules are histamine and bradykinin,
which dilate small blood vessels and constrict smooth muscles, particularly
in the bronchial tubes. The granules also contain heparin (which
prevents blood coagulation), enzymes that break down proteins, chemotatic
factors that attract eosinophils and neutrophils, and substances
that cause platelets to adhere to blood vessel walls and constrict
arteries.
The stimulated mast cells produce prostaglandins
and leukotrienes that cause capillaries to leak, smooth muscles
to contract, granulocytes to move actively, and platelets to become
sticky. The result of an antigen-IgE-mast cell reaction is acute
inflammation with dilation of the blood vessels and local seepage
of fluid from those vessels, later followed by an influx of granulocytes.
The granulocytes that move from the inflammation site can release
their own inflammatory mediators hours after the initial reaction.
If the antigen enters the eyes and nose, it causes
swelling and redness of the linings of the eyelids and nasal passages,
secretion of tears and mucus, and sneezing—all symptoms of
hay fever. If the antigen penetrates the lungs, the linings of the
bronchial tubes swell and secrete mucus while the muscles constrict,
narrowing the tubes and making breathing difficult—symptoms
of asthma. If an antigen gets into the bloodstream and interacts
with basophils as it does with mast cells, the release of the chemical
mediators causes systemic reactions such as hives and rashes. The
reaction is shown to the right.
In a milk allergy, the milk protein initiates an
immune response. In the intestines, the release of mediators from
mast cells causes diarrhea, cramps, vomiting, bleeding, inflammation,
or protein-losing enteropathies. The localized reaction increases
permeability of the gastrointestinal (GI) tract, making it likely
that the antigen will enter the body and end up in the bloodstream,
causing systemic manifestations that can range in severity from
hives to anaphylaxis. (Anaphylaxis is an immediate response to an
antigen, causing a drop in blood pressure and difficulty breathing.
If not treated, it can be fatal.
Why some people get allergies and others do not
appears to be related to the patient’s genetic predisposition,
exposure to food and other allergens, and the state of the GI barrier.
Food allergies appear to be an excessive response of the immune
system. Some people are more predisposed to producing IL-4, which
increases IgE production and the sensitization of mast cells.
Some people may not develop allergies until there
are changes in the structure of function of the GI tract. Any disruptions
of the GI barrier—caused by an immature GI tract, inflammation,
stress and destruction of villi and microvilli, viral gastroenteritis,
or the presence of malnutrition—increase GI permeability,
allowing antigens to enter the body.2 The antigens are able to enter
the lymphatic vessels, gaining entry to the entire body, where they
create an allergic reaction.
Types of Allergies
There are four types of immunological allergic reactions, shown
at the left.
Type I, an immediate hypersensitivity reaction,
is IgE-mediated. Known as atopy or anaphylactic hypersensitivity,
this is most common and best understood. It is described above in
the example of a milk allergy.
Type II reactions do not usually occur with food
antigens. They are antibody-mediated and cytotoxic. The activation
of complement causes much of the damage. This type of reaction occurs
in blood transfusions where the recipient has antibodies to the
transfused red cells.
Type III reactions involve immune complexes, with
damage caused by the activation of complement in response to antigen-antibody
complexes that have been deposited in the tissues or walls of the
blood vessels. These immune complexes settle into the vascular wall
and harm the tissue. The damage results from the complement and
the influx and activation of neutrophils and macrophages which release
bactericidal enzymes and IL-1. This type of reaction may play a
larger role than once thought in the development of allergic reactions
that may not directly involve IgE.
Type IV reactions, T cell-mediated delayed hypersensitivity
reactions, involve T cells interacting directly with antigens. Host
cells can be injured due to the release of chemicals from cytotoxic
cells and the production of cytokines, resulting in inflammation
and scarring.
Prevalence of Allergies
Accurate statistics on food allergy are difficult to obtain. As
many as one-third of consumers in North America and Europe believe
they have food allergies.3 However, the literature suggests that
true food allergy (defined as an immediate, IgE-mediated Type I
hypersensitivity reaction) is uncommon.
Based on double-blind, placebo-controlled food challenges,
skin tests, and blood tests to detect antifood antibodies, the consensus
seems to be that food allergy affects up to 8% of children under
the age of 5 and 1% to 2% of the adult population.4,5 Food allergy
is more common in children than adults, and the majority of food-allergic
children experience symptoms of food-related allergy during the
first year of life. Most food-allergic children outgrow their early
food allergies, especially to cow’s milk and egg proteins,
by roughly the age of 5, but some IgE-mediated food allergies may
persist throughout life.5
It is estimated that 30,000 individuals require
emergency department treatment for food allergies and 150 die from
allergic reaction to foods each year.6 In 2004, it was estimated
that 2.3% of the general population (approximately 6.6 million Americans)
had either physician-diagnosed and/or convincing seafood allergy.7
The most severe allergic response—life-threatening
anaphylactic reaction, mediated by a Type I hypersensitivity reaction—is
rare. Roughly 100 fatal cases of food-related anaphylaxis occur
in the United States each year.8
Statistical studies of the incidence of food allergy
may not be representative of the incidence of adverse reactions
to foods that are mediated by mechanisms other than Type I hypersensitivity.
In adults, non–immune-mediated intolerance seems to be much
more common than food allergy. Due to the lack of definitive objective
tests, it is not possible to provide reliable statistics. Some practitioners
estimate that up to 50% of the total population may experience some
degree of food-related reactions.
Allergenic Foods
Although any food protein can be potentially allergenic, relatively
few are known to cause most allergic reactions. In addition, an
allergenic protein can only induce an allergic reaction in an atopic
person who has been sensitized to it.
Most severe allergic reactions to foods occur in
response to a surprisingly small number of foods. The foods most
commonly associated with allergic reactions in children are milk,
egg, wheat, soy, peanut, tree nuts, fish, and shellfish.9 The incidence
of peanut allergies is significantly on the rise, causing concern
in schools. Allergies to milk, egg, wheat, and soy are usually outgrown
in early childhood. Adults often experience allergic reactions to
the foods that tend to persist as allergens beyond infancy; these
are peanuts, tree nuts, eggs, shellfish, and certain species of
fish.9
Lists of the most allergenic foods vary according
to the source of the data. In general, the “top eight”
are peanut products; soy products; egg products; milk products;
tree nut products—the most allergenic of these are almond,
Brazil nut, cashew, filbert (hazelnut), macadamia, pecan, pine nut,
pistachio, and walnut; fish products (some species); shellfish—crustaceans
(shrimp, prawn, lobster, crab, crayfish) and mollusks (clams, mussels,
oysters, scallops); and wheat products.10,11
However, the severity of reactions associated with
these foods varies. For example:
• Peanuts, tree nuts, shellfish, fish, milk,
and egg account for most reported cases of anaphylactic reactions
in children and adults.
• Soy is less frequently reported as a highly
allergenic food, although it is often associated with severe cases
of allergy and atopic dermatitis in childhood.
• Gluten allergy (quite distinct from gluten-sensitive
enteropathy or celiac disease, which is not considered an allergic
condition) is usually mild and is omitted from many “top allergen”
lists.
Other allergenic foods, present on some lists and
absent on others, include sesame seed and products containing sesame
seed, mustard seed, cod, and corn.
It is known that more adults are becoming truly
allergic to foods during their middle and later years—why
is still unclear. In adults, the most serious allergies are caused
by shellfish and nuts. Other foods that may cause allergies include
tomato, mushroom, carrot, celery, corn, chicken, orange, pineapple,
kiwi, garlic, yeast, food colors, and preservatives. This is by
no means a complete list.
Symptoms
Diagnostic and statistical difficulties arise from the differing
opinions as to what symptoms should be classified as allergic in
origin.
Atopy is an inherited set of symptoms, involving
IgE, that includes upper respiratory problems, rhinitis (dripping
sinuses), and skin rashes. A child’s chances of inheriting
atopy are 58% when both parents are atopic, 38% when one is atopic,
and 12.5% if neither parent is atopic.
Symptoms from a food allergy may appear immediately
following ingestion or up to five days after eating an allergic
food, which further complicates diagnosis. Many symptoms involve
the GI tract, particularly the intestine, as it comes in contact
with the antigens. These symptoms—diarrhea, constipation,
cramps, bleeding, ulcerations, inflammation—may or may not
be an allergic reaction. GI disturbances occur in 70% of patients
with allergies.
Skin rashes, including eczema and hives, are common
food allergy symptoms and occur in 24% of all patients. Twelve percent
of school-age children suffer from eczema due to food allergies.
Respiratory symptoms, including asthma and rhinitis, appear in only
4% of patients with food allergies.
Researchers have found that food allergies can induce
asthma. In a small number of people, food allergies cause bronchoconstriction
and increased airway hyperresponsiveness, both symptoms of asthma.12
Treating the food allergies appropriately may help control asthma.
Diagnosing Food Allergies
It is a misconception that a positive reaction to a skin test is
a positive diagnosis for a food allergy. A positive test may not
be associated with symptoms.2 Included in the assessment for food
allergies are health history, history of the symptoms and the suspected
foods, physical examination that includes anthropometric assessment
of growth and clinical symptoms of allergies, two-week food and
symptom diary, immunological testing involving skin tests or radioallergosorbent
tests (RASTs), trial elimination diet, and food challenges.
A thorough history includes suspected foods, symptoms,
when the symptoms occur and how much food it takes to bring them
on, and a health history, with emphasis on a family history of allergies.
A physical assessment, including anthropometric assessment of nutritional
status, growth and development in children, and allergic symptoms
is next. A two-week food diary is kept, including foods eaten, the
amount, time of appearance of symptoms, and any medications taken.
Once the list of suspected foods is drawn up from
the diet diary, specific tests can be done. The most reliable tests
are skin prick, RAST, and enzyme-linked immunosorbent assay (ELISA).
The skin prick test is the least expensive and preferred method
to use, since the results of the RAST and ELISA test correlate with
the skin prick test. A RAST or ELISA test is done if there is risk
for an anaphylactic reaction that could endanger the person’s
life. A negative skin-test response rules out IgE-mediated allergic
reactions.
The skin prick test is done by scratching the skin
with the suspected allergen and looking for a red wheal, indicating
an immune response. This test may overdiagnose food allergies and
should be followed by a food challenge. In a RAST, small samples
of blood are mixed with food extracts and washed with radioactively
labeled IgE. If the person is allergic to the food, measurable levels
of IgE antibodies can be detected. The ELISA test is similar to
the RAST, except it does not use radioactively labeled material.
The foods that test positive are included in a food
challenge. All foods known or suspected to cause an allergic reaction
are eliminated from the diet. After two to four weeks, when all
symptoms have disappeared, foods are reintroduced at a rate of one
per week to determine the allergenic foods.
The best method to determine a food allergy is a
double-blind challenge. The patient is given a capsule, not knowing
whether it contains food or a placebo. Up to two-thirds of people
who claim adverse reactions to food cannot reproduce the symptoms
on a double-blind challenge. While this figure may seem high, it
does point to the problem of psychologically induced food allergies.
Belief in an allergy can cause symptoms.
Nonimmunologic Reactions to Food
Lactose intolerance is the most common nonimmunologic adverse reaction
to food and is often confused with milk allergy. In the intestines,
a deficiency of the lactase enzyme, necessary to digest lactose,
may cause diarrhea, cramps, flatulence, and bloating.
Pharmacological agents found in food—vasoactive amines—may
precipitate an adverse food reaction. Histamine—found in fermented
cheeses, other fermented foods such as sauerkraut, anchovies, mackerel,
sardines, and canned tuna—can cause headaches, decreased blood
pressure, and asthma or allergylike symptoms. Phenylethylamine,
found in aged cheeses, red wine, and chocolate, can cause migraine
headaches. Histamine-releasing agents, found in shellfish, chocolate,
strawberries, tomatoes, peanuts, pork, wine, and pineapple, cause
the body to release histamine, causing urticaria, eczema, and other
allergylike symptoms.
Additives are more controversial. Whether they cause
reactions, and the scope of the problem, is debated. Some additives
have been recognized as causing reactions and others have not. Considering
the number of additives used and the endless combinations found
in foods, you can see the difficulty of determining the effects
of a single additive or synergism between additives.
Sulfiting agents used by the food and beverage industry
include sodium sulfite, potassium sulfite, sodium metabisulfite,
potassium metabisulfite, potassium bisulfite, and sulfur dioxide.
They are used as sanitizing agents for food containers and equipment,
and as preservatives to reduce or prevent microbial spoilage of
food. Foods that may contain sulfites include wine, shrimp and other
seafood, potatoes, dried fruits and vegetables, salads, cider, and
vinegar.
In August 1986, the FDA banned the use of sulfiting
agents in fresh foods. Potatoes did not fall into that category
and remain a potential hazard, along with wine, dried fruits such
as apricots, lemon juice, maraschino cherries, fruit drinks, and
frozen avocados. Reactions to sulfiting agents include asthma, anaphylaxis,
and loss of consciousness. Reports of deaths prompted the FDA to
ban their use in fresh foods.
Treatment
The severity of the reaction to a food determines the best treatment.
Some people are so allergic that all traces of the food must be
eliminated. They need education in label reading to recognize unusual
sources of the offending food. For example, an allergy to corn means
no corn meal, corn sweeteners, or corn syrup.
If a person is allergic to a food, he or she may
be allergic to other foods in the same plant family. An allergy
to peanuts may mean an allergy to other foods in the pea (legume)
family, such as peas, black-eyed peas, beans (including green beans),
and lentils.
If the allergy is moderate or mild, it may be possible
to eat small amounts of the offending food without a reaction. In
this case, a rotation diet is best. Only one food per day that causes
a reaction may be eaten, every four or five days.
Eliminating offending foods from the diet will become
easier in 2006, thanks to the Food Allergen Labeling and Consumer
Protection Act (FALCPA) passed by Congress in 2004. FALCPA goes
into effect in January 2006 and requires manufacturers to clearly
label any food that contains one of the eight major food allergens:
milk, eggs, fish, shellfish, tree nuts (walnuts, almonds, pecans,
etc), wheat, peanuts, and soybeans. The label must contain the common
name of the food and indicate any major allergen used in spices,
flavorings, additives, and colorings. For instance, a food that
contains casein must indicate that the product contains “milk.”
Adequate nutrition can be a problem if too many
foods are eliminated. The diet should contain the appropriate amount
of protein, carbohydrate, fat, fiber, vitamins, and minerals. If
eggs, wheat, milk, and beef are eliminated from the diet, it can
be a real challenge to meet daily requirements, especially for children.
The challenge in working with patients with food
allergies is to find substitutes that contain equivalent nutrients
to the eliminated foods and teach patients how to read labels, substitute
foods, and cook with unaccustomed foods.
— Dale Ames Kline, MS, RD, CNSD, is president
of Nutrition Dimension, Inc. A former hospital chief clinical dietitian
and nutrition educator in the Women, Infants & Children program,
she has written and edited continuing education home study courses
since 1984.
References
1. Lessoff MH. Food Allergy and Other Adverse Reactions to Food.
International Life Sciences Institute. Washington, D.C., 1994.
2. Chandra RK. Food hypersensitivity and allergic
disease: A selective review. Am J Clin Nutr. 1997;66:526S-9S.
3. Young E, Stoneham MD, Petruckevitch A, et al.
A population study of food intolerance. Lancet. 1994;343:1127-1130.
4. Sampson HA. Food allergy. Part 1: Immunopathogenesis
and clinical disorders. Current reviews of allergy and clinical
immunology. J Allergy and Clin Immunol. 1999;103(5
Pt 1):717-728.
5. Sampson HA, Burks AW. Mechanisms of food allergy.
Ann Rev Nutr. 1996;16:161-177.
6. USDA, CFSAN, Food Allergen Labeling and Consumer
Protection Act of 2004. Available at: http://www.cfsan.fda.gov/~dms/alrgact.html.
Accessed June 20, 2005.
7. Sicherer SH, Munoz-Furlong A, Sampson HA. Prevelance
of seafood allergy in the United States determined by a random telephone
survey. J Allergy Clin Immunol. 2004;114(1):159-165.
8. Sampson HA. Fatal food-induced anaphylaxis. Allergy.
1998;53:125-130.
9. Sicherer SH. Food allergy: When and how to perform
oral food challenges. Pediatric Allergy and Immunology.
1999;10:226-234.
10. Yeung JM, Appelbaum RS, Hildwine R. Criteria
to determine food allergen priority. J Food Protection.
2000;63(7):982-986.
11. Zarkadas M, Scott FW, Salminen J, et al. Common
allergenic foods and their labelling in Canada. Canad J Allergy
Clin Immunol. 1999;4(3):118-141.
12. Rumsaeng V, Metcalfe DD. Asthma and food allergy.
Nutr Rev. 1998;56(1 Pt 2):S153-S160.
Adverse Reactions to Food
Allergy (Immunologic Reaction)
• Type I — Immunoglobin E (IgE)-mediated
• Type II and Type III — IgG-mediated (IgM occasionally)
• Type IV — T cell-mediated
Food Intolerances (Nonimmunologic reaction)
• Metabolic: enzyme deficiencies such as lactase
• Toxic reactions: foodborne illnesses
• Sensitivity to additives or pharmacologic agents in food:
MSG, sulfites, histamine, tyramine, and tartrazine and other food
colors
Examination
1. A Type I hypersensitivity reaction to food is mediated by:
a. immunoglobulin G.
b. immunoglobulin E (IgE).
c. immunoglobulin M.
d. complement.
e. All the above
2. A Type I hypersensitivity reaction is triggered
by which of the following component(s) of food?
a. disaccharides
b. fatty acids
c. peptides
d. glycerol
3. The clinical symptoms associated with an immunological
allergic reaction—hives, itching, rashes, wheezing—are
caused by:
a. a decreased immune response.
b. the release of hormones that alter immune function.
c. an understimulation of B cells producing too few antibodies.
d. the release of chemical mediators histamine, complement, and
inflammatory mediators.
e. an overproduction of interleukin-1 (IL-1).
4. The subclass of T helper cells responsible
for the production of IgE is:
a. T helper 1 (Th1) cells.
b. Th2 cells.
c. T killer cells.
d. cytotoxic T cells.
5. Which of the following is not one of the foods
most commonly associated with allergic reactions?
a. Peanuts
b. Shellfish
c. Milk
d. Egg
e. Oats
6. A child’s chances of inheriting atopy
if one parent is atopic is:
a. 10%.
b. 16%.
c. 27%.
d. 38%.
e. 58%.
7. A nonimmunologic reaction to foods includes
which of the following?
a. Lactose intolerance
b. Sensitivity to food additives
c. Foodborne illness
d. Sulfite sensitivity
e. All the above
8. The best method of determining whether a person
has a true food allergy is which of the following?
a. A diet diary
b. Elimination diet
c. Diet challenge
d. Skin test
e. Double-blind food challenge
9. If a mild food allergy is diagnosed, all allergic
foods must be completely eliminated from the diet.
a. True
b. False
10. The Food Allergen Labeling and Consumer Protection
Act of 2004 requires manufacturers to do which of the following?
a. Remove all potentially allergic ingredients from their foods.
b. List all ingredients that have any allergic potential on the
food label.
c. List any of the eight major food allergens in common terms on
the food label.
d. List the quantity, in common terms, of any of the eight major
food allergens on the food label.
e. C and D
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