CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2010;8:755–759
EDUCATION PRACTICE
A 41-Year-Old Woman With Abdominal Complaints: Is It Food Allergy or
Food Intolerance? How to Tell the Difference
MARISA A. DEGAETANI and SHEILA E. CROWE
Department of Medicine, University of Virginia, Charlottesville, Virginia
This article has an accompanying continuing medical education activity on page e97. Learning Objectives—At the end
of this activity, the learner should be able to understand the different types of reactions to foods, clinical features
suggesting food allergy, and an algorithm for managing individuals with symptoms due to food ingestion.
Podcast interview: www.gastro.org/cghpodcast.
Clinical Scenario
A 41-year-old woman is referred to you for complaints of in-
termittent nonbloody diarrhea, abdominal cramping, and
bloating. Her symptoms tend to occur shortly after eating, and she
believes they might be triggered by dairy products. She also
notes that soon after eating tomatoes she develops itching and
swelling of her lips. Her past medical history is significant for
eczema as a child, with skin testing that showed reactivity to
cow-milk protein. She was told she would outgrow these food
allergies and currently she suffers from seasonal rhinitis and
similar symptoms when she mows the grass. She denies weight
loss, fevers, rash, wheezing, and arthralgias, but notes decreased
energy and headaches. Her physical examination is unremark-
able. She is concerned that she may be suffering from a food
allergy, and you wonder how to best evaluate and treat her for
possible adverse reactions to food.
The Problem
The patient’s clinical presentation is relatively nonspecific,
and thus the differential diagnosis is broad. Possibilities could
include food allergy, lactose intolerance, a functional gastrointes-
tinal (GI) disorder, eosinophilic gastroenteritis, a psychological
reaction to certain foods, and celiac disease. Adverse reactions to
food (ARFs) are common, with at least 20% of the population in
industrialized nations reporting such reactions. ARFs can be di-
vided into 2 categories: immune-mediated and nonimmunologic
(food intolerance). A majority of ARFs are nonimmunologic in
origin with lactose intolerance being the most common ARF
worldwide. Other causes of non–immune-mediated ARFs include
food toxicity, anaphylactic or pseudo-allergic reactions to food or
food additives, pharmacologic reactions to food or food additives,
physiologic food intolerance, and psychologic reactions to food.
This last category is not covered here because it is beyond the scope
of this article. Immune-mediated reactions causing GI complaints
include immunoglobulin (Ig)E-mediated food allergy, as well as
allergic eosinophilic GI syndromes. Also in this category are food
protein–induced enterocolitis syndromes and celiac disease; how-
ever, these latter 2 disorders are not discussed further in this article
because food protein–induced enterocolitis syndromes occur in
young children and celiac disease is a subject unto itself.
Immune-Mediated Adverse Reaction to Food
Food allergy. Food allergy results from IgE-mediated
reactions, also known as type I hypersensitivity reactions. These
antibodies, which bind to specific food proteins, can degranu-
late mast cells and basophils, which then release mediators such
as histamine, leading to symptoms of food allergy. Food allergy
occurs in approximately 4% to 8% of children and in approxi-
mately 1% to 4% of adults in the United States and appears to
be increasing in prevalence. The foods implicated most com-
monly in food allergy include cow’s milk, eggs, peanuts, sea-
food, and shellfish. Allergic reactions to food often occur in
early childhood and typically disappear spontaneously by 4 to 6
years old. Few children retain their food allergy into adulthood,
which accounts for the decrease in prevalence between children
and adults noted earlier. Some adults, however, develop food
allergy without experiencing a food allergy in childhood.
The symptoms of food allergy cover a wide spectrum ranging
from minor complaints to life-threatening anaphylactic shock
(Figure 1). Approximately 50% of patients suffering from food
allergy have some type of GI manifestation, and in about one third
of patients with food allergy, GI symptoms are the predominate
complaint. The diagnosis of food allergy that manifests solely in
the GI tract can be difficult, especially because the symptoms tend
to be nonspecific and current diagnostic tools have limited accu-
racy. Although patients with complaints related to food often are
thought to have functional GI disorders, further evaluation should
be considered because food allergy is not rare and may coexist with
other GI conditions. It is worth noting that food allergies have
replaced drugs and insect venom as the most common cause of
life-threatening anaphylaxis in industrialized countries. Individu-
als who are at increased risk of anaphylaxis include those with a
past history of anaphylaxis, reactions with respiratory symptoms,
or reactions after the ingestion of peanuts, tree nuts, fish, or
seafood, or those who are taking ␤-blockers or angiotensin con-
verting enzyme inhibitor therapy.
Within the category of food allergy there are 2 specific presen-
tations that deserve mention: the pollen food syndrome and the
latex–food allergy syndrome. The pollen food syndrome is the
most common manifestation of food allergy in adults. In this
syndrome cross-reactivity occurs between pollen-specific IgE and
homologous proteins found in fresh fruits and vegetables. Com-
mon associations include birch pollen IgE reacting with apple,
pear, carrot, and celery; mugwort pollen IgE reacting with celery
Abbreviations used in this paper: ARF, adverse reaction to food; GI,
gastrointestinal; Ig, immunoglobulin.
© 2010 by the AGA Institute
1542-3565/$36.00
doi:10.1016/j.cgh.2010.03.023
756 DEGAETANI AND CROWE
and spices; and grass pollen IgE reacting with fig, tomatoes, and
melon. Usually the sensitivity to pollen manifests first. Exposure to
the cross-reacting foods then may lead to pruritis, tingling, and/or
swelling of the tongue, lips, palate, or oropharynx. Rarely, nausea,
vomiting, diarrhea, bronchospasm, or anaphylaxis can occur
shortly after ingestion of the allergen. The potential causes of these
reactions can be evaluated by skin-prick testing using extracts of
the implicated fruits or vegetables.
Latex–food allergy syndrome, also referred to as the latex–
fruit syndrome, is reported to occur in up to more than half of
individuals with latex allergy. In such individuals, exposure to
certain foods such as banana, avocado, chestnut, and kiwi can
result in the same symptoms as if exposed to latex, ranging
from pruritis, eczema, oral–facial swelling, asthma, GI com-
plaints, and anaphylaxis. Of note, the prevalence of allergy to
latex is increasing worldwide, which is likely to result in a
corresponding increase in this form of food allergy.
Eosinophilic gastrointestinal disorders. Eosino-
philic GI disorders are characterized by eosinophilic infiltration
of the GI tissue in the absence of other causes of eosinophilia such
as malignancy, parasites, collagen vascular disease, inflammatory
bowel disease, or drug sensitivity. Eosinophilic gastroenteritis can
involve any or all layers of the gut wall. With mucosal involvement,
abdominal pain, vomiting, and diarrhea are common symptoms.
Obstructive symptoms can be seen with muscularis involvement,
and bloating and ascites can be seen with serosal involvement.
Peripheral eosinophilia is seen in up to two thirds of patients. This
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 8, No. 9
Figure 1. Multisystem presen-
tation of food allergy. The multi-
ple targets of the immune re-
sponse to food allergy. The
manifestations can range from
atopic dermatitis to full-blown
anaphylaxis with respiratory and
cardiac involvement.
disorder is associated strongly with a history of food allergies. The
diagnosis is made by esophagogastroduodenoscopy with biopsy.
Elimination of offending foods can improve symptoms, and cor-
ticosteroids and cromolyn can be used for refractory disease. Eo-
sinophilic esophagitis can affect any age group but is seen more
frequently in younger males. Older children and adult patients
often present with symptoms of heartburn and dysphagia, whereas
younger children present more commonly with regurgitation,
vomiting, and abdominal pain. Again, the diagnosis is made by
esophagogastroduodenoscopy with biopsy. In addition to avoid-
ing culprit antigens, treatment includes topical steroids (swallow-
ing of inhaled formulations of steroids used in the treatment of
asthma), oral steroids, montelukast, and investigational therapies
including anti–interleukin-5 antibodies. Similar to patients with
eosinophilic gastroenteritis, patients with eosinophilic esophagitis
should be referred to an allergist to be evaluated for food allergy
with subsequent elimination of offending foods from the diet.
Non–Immune-Mediated Adverse Reaction to
Food
Food toxicity. Food toxins can occur naturally in cer-
tain foods, and when ingested frequently or in large amounts
symptoms can result. Examples include saxitoxin in shellfish,
which can cause paralysis, or vasoactive amines in a variety of
foods (discussed later). Other food toxins can result from food
processing and storage. For example, aflatoxins can be found in
peanuts contaminated by mold and can cause acute hepatic fail-
September 2010
ure. Food toxicity also can be the result of contamination by
microorganisms, including Escherichia coli, salmonella, shigella,
campylobacter, vibrio, and hepatitis A, as well as preformed mi-
crobial toxins, such as staphylococcal enterotoxins or botulinum
toxin. The Center for Disease Control and Prevention estimates
that about 25% of Americans get food poisoning every year, and
this acute illness may lead to postinfectious irritable bowel syn-
drome, with symptoms similar to idiopathic forms of irritable
bowel syndrome.
Carbohydrate intolerances. Disaccharide intoler-
ances result from deficiencies in the brush-border enzymes of the
small intestine that are necessary for carbohydrate metabolism,
and include intolerances to lactose and sucrose. Lactose intoler-
ance is very common, especially in people of Mediterranean, Afri-
can, Asian, and Native American heritage, resulting from a physi-
ologic decline in the levels of lactase with age. Secondary lactase
insufficiency can occur as a result of gastroenteritis, Crohn’s dis-
ease, or celiac disease. Sucrase–isomaltase deficiency usually pre-
sents in infancy with diarrhea and failure to thrive, but occasion-
ally is not diagnosed until adulthood. Symptoms of disaccharide
intolerances usually include bloating, cramping, flatulence, and
diarrhea shortly after ingestion of foods containing the culprit
sugar. Fructose, sorbitol, and other fermentable oligosaccharides,
disaccharides, monosaccharides, and polyols can lead to similar
symptoms in any individual when ingested in large enough quan-
tities because these poorly absorbed carbohydrates act as a sub-
strate for bacterial fermentation and also have an osmotic effect.
Physiologic reactions to food components or ad-
ditives. Many foods are associated with gas production, in-
cluding legumes, cabbage, bran fiber, and other vegetables and
grains. Heartburn and dyspepsia can result from food and food
additives that cause relaxation of the lower esophageal sphinc-
ter, as well as fatty foods that delay gastric emptying. Patients
with functional GI disorders often complain of more general
food intolerance symptoms such as exacerbations by large meals,
fatty foods, and eating out. However, such patients also can have
a specific ARF to food, and it is important to determine whether
specific food intolerances exist in this group of patients because
elimination of the offending food(s) can be beneficial.
Pseudoallergic reactions to food. Certain foods can
mimic the effects of mast cell degranulation but do not involve IgE
antibodies. These can include strawberries, chocolate, and toma-
toes, as well as additives such as salicylates (food preservatives),
benzoates (food preservatives used in pickles, alcoholic beverages,
and fruit drinks), and tartrazine (a synthetic yellow dye). In the
case of such food-induced reactions that are not immune-mediated,
skin and blood tests for food-specific antibodies will be negative.
Pharmacologic reactions to foods and food addi-
tives. This type of intolerance can be caused by both vasoac-
tive amines found in food, such as dopamine, histamine, sero-
tonin, phenylethylamine, and tyramine, and food additives,
such as sulfites, tartrazine, and monosodium glutamate. Vaso-
active amines are found in a wide variety of foods including
chocolate, wine, cheese, legumes, and fermented foods. Symp-
toms usually manifest outside the GI tract in the form of
headache, asthma, and urticaria. Some foods that contain his-
tamine, such as cheese, alcohol, fermented food, and spoiled
fish, can cause symptoms similar to those seen in an IgE-
mediated allergy. Histamine intolerance also can be seen in
individuals who are deficient in di-amino-oxidase, the enzyme
that deactivates histamine or those taking di-amino-oxidase–
GASTROINTESTINAL FOOD ALLERGY 757
inhibitor drugs. Food additives cause a wide variety of adverse
reactions including urticaria, asthma, dermatitis, headache, and
occasionally have been linked to anaphylaxis.
Management Strategies
Returning to our case presentation, an attempt must be
made to determine which type of ARF could be causing our
patient’s symptoms of diarrhea, cramping, and bloating. Un-
fortunately, there are limited diagnostic tools to evaluate ARF,
so differentiating among the various types can be challenging.
Obtaining a thorough medical history is very important. Clues
that would suggest a food allergy include young age of the patient
(⬍3 years old), history of acute reaction that occurs shortly after
ingestion of a specific food, non-GI manifestations such as wheez-
ing and urticaria, and associated atopic diseases (eczema, asthma,
and family history of atopy). Our patient has a few elements in her
history that are suspicious for food allergy: she has a history of
atopy as well as GI symptoms that occur shortly after ingestion
of specific foods such as dairy products and tomatoes. Given her
history of allergic rhinitis and possible grass allergy, the symptoms
of itching and swelling of the lips associated with tomato inges-
tion suggest a diagnosis of a pollen food syndrome.
Disaccharide intolerances also can be associated with acute
reactions after the ingestion of certain food(s). Lactose intolerance
should be considered in our patient because of her perceived
sensitivity to dairy products. Reactions to all dairy products (in-
cluding yogurts and certain cheeses that are naturally low in
lactose) are unlikely to be caused by lactose intolerance and sug-
gest other diagnoses, such as a functional GI disorder or, much
less likely, cow’s milk protein allergy (the latter is less common in
adults than children). Long-chain triacylglycerols found in milk,
cream, and other dairy products can be a factor in perceived
intolerance to dairy products. Of note, it is important to differen-
tiate true milk allergy from lactose intolerance because individuals
with lactose intolerance are not at risk for suffering severe ana-
phylactic reactions from ingestion of dairy products as their allergy
counterparts are. Moreover, naturally lactose-free dairy products,
which should not cause symptoms in those who are lactose intol-
erant, must be avoided with cow’s milk protein allergy.
After a complete history, further testing can include a com-
plete blood count with differential to measure the eosinophil
count, tissue transglutaminase IgA, lactose hydrogen breath
testing for lactose intolerance, and esophagogastroduodenos-
copy with mucosal biopsies to further evaluate for eosinophilic
GI disorders and celiac disease.
If food allergy is suspected, particularly with symptoms of
wheezing, difficulty breathing, pharyngeal edema, syncope, and
anaphylaxis, patients must be referred to an allergist for further
evaluation. Tests for specific IgE antibody, including radioaller-
gosorbent tests, enzyme-linked immunosorbent assays, and
skin-prick tests may be used in the diagnosis of food allergy. If
a positive test result correlates with clinical symptoms, a diag-
nosis of food allergy can be made. However, merely obtaining a
positive result on one of these tests does not necessarily warrant
removal of that food from the diet; clinical symptoms must be
present. Atopy patch testing for delayed immune reactions to
food also is starting to be used. In large academic institutions
and research centers, double-blinded placebo-control food chal-
lenges occasionally are used in research studies for diagnosing
food allergy, but this technique is not widely used in routine
practice. Once specific foods are identified, the patient should
758 DEGAETANI AND CROWE CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 8, No. 9

be referred to a knowledgeable dietician for further instruction Table 1. Hypoallergenic Diet

and to ensure adequate nutritional intake, particularly in young
Food category Allowed Avoid
patients and those with multiple food allergies.
If specific foods are not identified on initial history, we Meat and meat Lamb Pork
recommend that the patient keep a food diary for a period of alternatives Chicken Beef
several weeks in which all food and beverage intake is recorded Turkey Fish
along with any symptoms. In our experience, the food diary Eggs
may not identify specific foods as culprits but rather other Milk and milk products
dietary factors such as large meals, fatty meals, restaurant food, Seafood
Grains Rice (Barley) Wheat
or meals eaten close to bedtime as causing problems. In this
Oats
case, lifestyle changes including modification of eating habits Tapioca Corn
are the key to management of these patients. If specific foods Arrowroot Rye
are found to exacerbate GI symptoms, they should be removed Legumes and nuts Avoid all dried peas,
from the diet for 3 to 4 weeks to see if symptoms improve. If beans, nuts
symptoms improve, the patient may reintroduce the suspected Vegetables All except corn and
offending food(s), one item at a time, in an attempt to prove the peas
association. This type of open food challenge should be confirmed Fruits All except citrus
by another more objective method before the item is eliminated fruits, strawberries,
and tomatoes
permanently from the diet, especially if the patient is young and
Sweeteners Sugar (cane or beet)
the food item(s) is(are) a major component of the diet. Maple syrup
A so-called elimination, exclusion, or hypoallergenic diet (see Table 1 Honey
for an example) may be helpful if the food diary fails to identify Fats and oils Olive oil Soy, corn, peanut oils
food(s) or food additives. If symptoms improve on a restricted diet, Safflower oil Butter
new foods are introduced gradually into the diet in an attempt to Crisco Margarine
identify which foods could be causing the symptoms. Similar to Miscellaneous White vinegar Coffee, Tea
the food diary, in our experience the elimination diet is most Water (Ginger ale) Alcohol
useful in helping patients to realize that their symptoms are not Salt (Pepper) Chocolate
Fruit juices Colas
related to specific foods but rather to other factors including fatty
Spices
foods and large meals. Moreover, we find that some patients with
Chewing gum
functional GI conditions are able to tolerate certain foods previ-
ously thought to be a problem when they are re-introduced. NOTE. The hypoallergenic diet also is referred to as an exclusion diet. Foods
Management of all ARF, immune-mediated and non–immune- in parentheses may cause adverse reactions in some individuals. These
mediated, is based primarily on avoidance of the food or food foods may be omitted from the trial elimination diet. If an allowed food is one
additive identified as causing the symptoms, as well as being aware that has caused a reaction in the past, it also should be omitted. While on
the trial elimination diet, symptoms are recorded and a note should be made
of any cross-reacting food groups. New therapeutic approaches are
if there is any change from the previous regular diet. If there are symptoms,
currently under development for treatment of food allergy, al-
determine if there is any relationship to particular foods.
though there is no clear evidence as of yet that these approaches Reprinted with permission from Crowe and Bischoff (Gastrointestinal
are beneficial in the prevention or modulation of food allergy. food allergy: new insights into pathophysiology and clinical perspec-
Potential therapies for IgE-mediated food allergy include biologic tives. Gastroenterology 2005;128:1089 –1113).
therapy using anti-IgE antibodies, oral tolerance induction, and
systemic immunotherapy using mutated proteins in which the IgE Areas of Uncertainty
binding sites of the proteins are altered, preventing the IgE anti-
Despite their prevalence, adverse reactions to food remain
body from binding them and eliciting a reaction while allowing
poorly understood and not well studied. There are many areas of
recovery of the normal T1 helper cell milieu. Although these
uncertainty surrounding ARF, and it is clear that further research
approaches have promise, and some such as anti-IgE to peanuts
needs to be conducted in this field. Questions include the follow-
have shown benefit, further studies still are needed.
ing: (1) What explains the increasing prevalence of food allergies?
In instances of food allergy in which an elimination diet
(2) Can food allergies be prevented? (3) Why in a given individual
cannot be adhered to or when one is unable to identify specific
can tolerance disappear at a given time and why with some foods
foods allergens, antihistamines and oral sodium cromoglycate
can tolerance naturally reappear? (4) Among thousands of food
are used to help reduce symptoms, but their efficacy is un-
proteins, why do only a relatively small number seem to induce
proven. In more severe cases of food allergy, therapy with
IgE-dependent allergic reactions? (5) How can one confirm the
corticosteroids may become necessary. Because it often is diffi-
diagnosis of food allergy on an objective basis? (6) What treatment
cult to prevent accidental exposure to food antigens, patients
alternatives are there to food antigen avoidance? Until we have
with a history of an anaphylactic reaction should be instructed
better understanding of this field, the present management strat-
to carry an epinephrine-containing syringe for emergency ad-
egy revolves primarily around food allergen avoidance.
ministration, and because reactions may be biphasic in nature,
patients must be instructed to go to a local emergency facility
after the initial symptoms. Again, we emphasize that referral to Published Guidelines
an allergist and a dietician who specializes in food allergies is In 2001 the American Gastroenterological Association pub-
necessary because gastroenterologists do not have sufficient lished recommendations for the management of food allergy. Our
training or expertise in food allergy and its management. approach in following these guidelines is summarized in Figure 2.
September 2010 GASTROINTESTINAL FOOD ALLERGY 759

Figure 2. Algorithm for the manage-

ment of food allergy. *Testing indicates
skin-prick testing, radioallergosorbent
tests (RAST), IgG4 assay, and/or patch
testing. Note that clinical symptoms
must be associated with the food(s) that
test positive before the food(s) should
be eliminated from the diet. **Oral food
challenge (OFC) involves reintroducing
the food and observing for signs/symp-
toms of food allergy (FA). For more infor-
mation on the hypoallergenic diet, see
Table 1. Treatment of food allergy
involves elimination of the causative
food(s) from the diet.

Recommendations for This Patient Suggested Reading

Our patient presented with nonspecific symptoms of di-
arrhea, cramping, and bloating. Given her association of these
symptoms with dairy products we decided to test for lactose
intolerance with a lactose hydrogen breath test, which was positive.
We also performed a complete blood count and eosinophil count,
and a total IgA and tissue transglutaminase IgA, all of which were
within normal limits. We then referred her to an allergist for
further evaluation of a possible pollen food syndrome given her
history of rhinitis and itching and swelling of the lips associated
with tomato ingestion. Her skin-prick test result was positive for
tomato, grass, and other plant pollens, confirming our impression.
Regardless of whether an adverse reaction to food is a true food
allergy or a food intolerance, the treatment is essentially the same:
elimination of the offending food. She was instructed by a dieti-
cian to avoid lactose-containing dairy products as well as toma-
toes, educated on the cross-reactivity of grass pollen with tomato
10. Crowe SE, Bischoff SC. Gastrointestinal food allergy: new in-
and other foods, and also referred to the Food Allergy and Ana-
phylaxis Network (www.foodallergy.com) for additional informa-
tion and guidance about food allergies.
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4. Sampson HA. Food allergy. J Allergy Clin Immunol 2003;111:
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Supplementary Material
Note: To access the supplementary material accompa-
nying this article, visit the online version of Clinical Gastroenter-
ology and Hepatology at www.cghjournal.org, and at doi:10.1016/
j.cgh.2010.03.023.
Reprint requests
Address requests for reprints to: Sheila E. Crowe, MD, Department of
Medicine, University of Virginia, Charlottesville, Virginia 22908-0708.
e-mail: scrowe@virginia.edu; fax: (434) 982-0044.
Conflicts of interest
The authors disclose no conflicts.