General

1. A food allergy is the immune system's reaction to a certain

food, when the body creates IgE antibodies to that food. When
these IgE antibodies react with the food, histamine and other
chemicals (called mediators) are released from various cells
within the body. These mediators cause hives, asthma, or other
symptoms of an allergic reaction.
2. Eight foods cause 90% of all food allergic reactions. They are
milk, egg, wheat, peanut, soy, tree nuts, fish, and shellfish.
3. There is no cure for food allergies. Strict avoidance (by reading
ingredient listings all the time) is the only way to prevent a
reaction.
4. Children with asthma and food allergies are at increased risk for
a severe reaction.
5. Symptoms can include: vomiting, diarrhea, cramps, hives,
swelling, eczema, itching or swelling of the lips, tongue or
mouth, itching or tightness in the throat, difficulty breathing, or
wheezing.
6. Allergic symptoms can begin within minutes to 1 hour after
ingesting the food.
7. Milk is the most common cause of food allergies in children.
Other foods most commonly cited are eggs, wheat, peanut, soy
and tree nuts.
8. Peanuts, nuts, fish, and shellfish commonly cause the most
severe reactions.
9. Up to 5 percent of children have food allergies.
10. Most children outgrow their allergy, although an allergy to
peanuts and tree nuts is considered life-long.

How Little Does it Take?

1. As little as 1/2 a peanut can cause a fatal reaction for severely
allergic individuals.
2. Some severely milk-allergic children can have a reaction if milk
is splashed on their skin.
3. Being kissed by someone who has eaten peanuts for example,
can cause a reaction to severely allergic individuals.

Anaphylaxis Facts

1. Anaphylaxis is a sudden severe potentially life-threatening

allergic reaction. It can be caused by food allergy, insect stings,
or medications.
2. Although any food can potentially cause anaphylaxis, peanuts,
nuts, shellfish, fish and eggs are foods that most commonly
cause this reaction.
3. As little as 1/5 of a teaspoon of the offending food has caused
death.
4. Symptoms can include hives, swelling (especially of the lips and
face), difficulty breathing (either because of swelling in the
throat or an asthmatic reaction), vomiting,diarrhea, cramping,
and a fall in blood pressure. They can occur in as little as 5 to 15
minutes.

Food Allergy Myths

1. Myth: A recent study showed that up to 25 percent of adults
believe they have food allergies. Scientific studies show,
however, that only 1 to 2 percent of adults truly have a food
allergy.
2. Myth: Food allergies are not real. Not true. An allergic
reaction involves the body's immune system. In the case of food
allergy, the immune system misinterprets a food as a harmful
invader and releases histamine and other chemicals to protect
the body from harm. Symptoms can include hives, vomiting,
diarrhea, and respiratory distress.
3. Myth: Food allergies should not be taken seriously. Every
year more people die of food allergic reactions, than allergic
reactions caused by insect stings. Food allergies must be taken
seriously.
4. Myth: Food additives and artificial flavors cause the
majority of food allergic reactions. Contrary to common
belief, natural foods account for the majority of allergic
reactions. The foods that most commonly cause reactions are:
peanuts, milk, eggs, wheat, soy, tree nuts (almonds, walnuts,
pecans, etc.), fish, and shellfish. These foods may appear in
foods as ingredients or under natural flavors.
Last modified on 2/1/99.

This information has been written as a general information resource. It is not intended for use in diagnosis, treatment, or any other
medical application. Questions should be directed to your personal physician. There is no warranty on this information and no

liability is assumed by the author or any group for the recommendations, information, dietary suggestions, menus, and recipes
promulgated. Products mentioned or omitted do not constitute endorsement.

It is important to know the difference between a food allergy and a food intolerance. Although these
words are used almost interchangeably, they are two very different things.
FOOD ALLERGIES
A food allergy occurs when the body's immune system reacts to a food protein, and triggers an allergic
reaction, causing the persons antibodies to attack the foreign substance. An allergic reaction may show up
immediately or several hours after the food is eaten.
Symptoms of a food allergy may include hives, eczema, itching, swelling of the throat, coughing, sneezing,
nasal stuffiness, vomiting, diarrhea, cramping, and in severe cases, even death.
FOOD INTOLERANCE
A food intolerance is an adverse reaction to a food that does not involve the immune system. Although many
of the symptoms are the same as a food allergy, it is important that you consult your physician to determine
the severity of your condition.
Some food intolerances can be caused by disease. (see our section titled Celiac Disease)
FOODS COMMONLY CAUSING ALLERGIES/INTOLERANCES

Milk (lactose intolerance)

Wheat
Peanuts
Fish

Soy
Barley
Rye

Oats

Eggs

Milk
Allergens available for IgE antibody
measurement

f76

a-lactalbumin

f82

Cheese, mold

f77
f231
f78
f81

B-lactalbumin
Boiled cow's
Casein
Cheese, Cheddar-type

f2
Rf300
Rf286
Rf236

Cow's milk
Goat's milk
Mare's milk
Whey

Milk Allergy
Meat and dairy products have several things in common. Nutritionally they have
been regarded as the main protein sources for man in western civilization in the
proportion of meat, about 35% and dairy products, 25%. In the food processing
industry, dairy products and meat products are often combined. Milk lactose is
often included in processed meats for flavor and milk protein as sodium
caseinate is added as an emulsifier. Such processed meats include frankfurters,
Vienna sausages, mortadella, luncheon meats, chicken sausages and pates.
Caseinate is added to ham brines for injecting to improve slicing ability. Beef,
mutton, chicken fat and pork fat are easier to emulsify with the help of sodium
caseinate.
Chicken soup served in a hospital to a child with cow's milk allergy caused near
fatal anaphylaxis. The soup contained sodium caseinate. The hospital staff did
not recognize this as a milk protein. Furthermore, the staff was unaware of the
difference between lactose intolerance and milk protein allergy and considered
reactions to milk to be relatively harmless. The child was saved because the
mother recognized the early phase of the reaction and proper treatment could be
given (37).
Undeclared additives are commonly found in food products on the market. The
reason varies from illegal substitution for higher priced ingredients to unintended
contamination during food processing.
Over a 3-year period, 18 situations with discrepancies between contents and
label were confirmed by the Swedish National Food Administration (26). In 13
cases, the investigation was initiated because of reactions observed by
individuals with known disease. In 3 cases, the dose of allergen leading to the
reaction could be estimated. Both 6mg hazelnut and milk corresponding to 10mg
casein caused reactions requiring medication. A meal of sausage containing the
amount of cow's milk equivalent to about 60mg casein resulted in fatal
anaphylaxis

Cow's Milk
skimmed cow's milk
Cow's milk is a major cause of adverse reactions in infants. Cow's milkinduced asthma is often observed in infants with food hypersensitivity. In
fact, asthma has been noted in 7-29% of those sensitive to milk (6). Milk is
often described as a cause of rhinoconjunctivitis in young children and a
role for food allergy in serous otitis media has also been proposed (6).
Cow's milk allergy in infants has a much better prognosis than in older
children or adults (3). Olalde et al. (29) reported onset of IgE-mediated
allergy in a patient aged 29.
Diversity in food processing
Milk and milk derivatives are used in a wide variety of confectionery
products. Caramel flavor is best developed from sweetened condensed
milk. Caseins help enhance moisture retention in candy. Hydrolyzed milk
proteins are whipping agents for frappes and marshmallows. In baked
goods milk improves the crust color, resilience, and the strength of cakes
and cookie dough.
Cases of allergic reactions to nondairy or pareve products (no milk or
meat) containing milk proteins either through contamination during
processing or addition of sodium caseinate have been reported (15).

Clinical experience
In a recent study in Japan using Pharmacia & Upjohn, Diagnostics CAP
System, the clinical sensitivity was 95 % and specificity was 93% for milk
(28).
Businco et al. (8) found that cow's milk-allergic children developed IgE
antibodies to milk, as measured with Phadebas RAST, before onset of
clinical allergy, indicating in vitro measures can be good predictive tools.
Symptoms
The symptoms in infants are usually gastrointestinal (GI) and
dermatological with dermatitis often appearing early. Foucard describes
two different groups of infants; those who react immediately with GI
symptoms and urticaria and who are often atopic with positive findings in
skin prick test and RAST; and, the late responders who may be governed
by a non-IgE-mediated allergy (14).

In children retaining milk allergy, cutaneous symptoms decrease while

respiratory and GI symptoms increase with age (4-14 years) (2,22).
Infants with early sensitization to cow's milk proteins have an increased
risk for later development of other food allergies and sensitization to
inhalant allergens (7,21).
Prevalence
Reports of prevalence range from 1.97.5% of all infants during their first
year (3). Some patients retain the lifelong allergy (24). May et al. (27)
found that children hypersensitive to another food were likely to have a
greater antibody production to milk than those children who were not
hypersensitive.
Prevention
There are many studies supporting avoidance of cow's milk and prolonged
breastfeeding as preventive measures. In a report of a prevention program
in Denmark, breastfeeding or a hypoallergenic formula and avoidance of
other foods during the first six months of life had a protective effect (1).
The authors reviewed 20 prospective studies almost all of which showed a
reduction of atopic dermatitis and wheeze when preventive measures
were taken (17). In a follow-up study of the effects of maternal antigen
avoidance after four years, the authors found avoidance of cow's milk, fish
and egg during the first three months of lactation decreased both the
current prevalence and the cumulative incidence of AD at age four in
atopic children (38).
Allergen composition
There are many proteins in milk; five are of major interest. These include:
bovine serum albumin, gamma globulin, a-lactalbumin, i3-lactoglobulin
and casein. Reactions to separate proteins are uncommon. Ordinary
industrial treatment of milk does not remove proteins and only partially
reduces the allergenicity.
Crossreactivity
There is crossreactivity between cow's and goat's milk as these animals
are members of the same family ( 1 6). Traces of penicillin in milk can
cause reactions in sensitive patients. Sensitivity to cow's milk does not
usually presume sensitivity to beef or inhalation of cow dander. It is
thought that there are unique heat-labile fractions in beef which may
explain the differing clinical responses to raw and well-cooked beef in
some milk-allergic patients (42).

Boiled cow's milk

Boiling is known to reduce the allergenicity of the whey proteins but not
casein and thus could be used to test whether a cow's milk-sensitive
patient is likely to tolerate cooked or baked milk products.

a-lactalbumin
a-lactalbumin is regarded as one of the major cow's milk allergens.
Hoffman et al. (19) found 12/25 eczema patients (48%) Phadebas RASTpositive to alactalbumin. A study of 25 milk-allergic patients with a variety
of allergic symptoms showed a-lactalbumin specific IgE antibodies in 67%
of the sera (33).

B-lactoglobulin
B-lactoglobulin is a major whey protein of milk which together with a
lactalbumin is regarded as a major allergen in cow's milk. The allergenicity
of B-lactoglobulin resists pasteurization A study of 25 milk-allergic patients
with a variety of allergic symptoms showed i3-lactoglobulin-specific IgE
antibodies in 33% of the sera (33).
In a study of 13 infants with atopic dermatitis, i3-lactoglobulin was
investigated in breast milk and in the infants' sera before and after
maternal elimination diet and after maternal challenge (10). In this study,
the authors showed that the food antigen was transported via breast milk
into the infants' circulation. In a review of breastfeeding and allergy, Zeiger
(45) pointed out that while b-lactoglobulin antigens are available in the
mother's breast milk with a potential to sensitize, actual sensitization has
not been conclusively documented. The level of specific IgE antibodies to
cow's milk was shown to decrease during elimination diets in patients with
atopic dermatitis induced by cow's milk (1).
James & Sampson (23) found that monitoring of B-lactoglobulin IgE
concentrations and calculating a ratio of IgE to IgG antibodies could be
useful in predicting which patients will ultimately lose clinical reactivity.

Casein
Caseinates are added to infant formula (9,30,36). Gern et al. (15) reported
casein as a cause of allergic reactions in patients eating so-called "nondairy" products. Casein and caseinates are used as extenders and
tenderizers in imitation sausages, leaves, soups and stews. It is often
used to nutritionally fortify foods and as a supplement because of the high
protein content and quality, the low level of lactose and the bland flavor.
Such nutritionally fortified foods include high-protein beverage powders,
fortified cereals, infant formula and nutrition bars. Other uses include
coffee whiteners, sauces, ice cream, salad dressing, formulated meats,
bakery glazes, and whipped toppings.
Casein makes up about 75-80% of all milk protein and is heat stable. The
concentration in cow's milk is between 2.5-3.2% or 3.2g per 100ml milk. It
was isolated from milk and has been marketed commercially since 1900.
Host (20) states that high pasteurization (120"C for 20 minutes) only
reduces but does not eliminate the allergenicity of the caseins. Note that
commercial pasteurization is often much shorter than 20 min.

Clinical experience
When studying 92 cow's milk-allergic patients, Bernard et al. (5) found that
there is a great variability in the specificity and intensity of IgE response to
the four major casein fractions: aS1; 13, aS2; and K indicating presence of
distinct epitopes on the individual casein molecules.
In a case study of a 29-year old becoming suddenly allergic to cow's milk,
the patient also had skin sensitivity to casein in skin prick test (29).

Cheese, Cheddar-type
Hippocrates may well have been the first to describe intolerance to
cheese. The making of cheese predates biblical times and innumerable
varieties are commercially available. Rennet cheeses such as Cheddar,
and other types of hard cheeses ripen with the help of bacteria. Cheese
analogs (imitation products) are all based on casein as a protein source.
Some soybean protein isolates have been used as protein extenders in
cheese replacing up to the 30% of the casein.

Clinical experience
Skin reactivity to cheese has been reported (43). A non-immune response
to cheese may be caused by tyramine especially in cases of chronic
urticaria (12). Cheeses may also be rich in histamine (40). In a recent
review of atopic food allergy cheese was the third most important allergen;
12.9% of 402 predominantly adult patients with confirmed food allergy
(44).

Cheese, mold
A mixture of white soft cheeses, Camembert and Brie, Gorgonzola and
Roquefort. All types contain molds belonging to the genus Penicillium.
Generally, sera from patients allergic to inhaled mold spores (Aspergillus,
Alternaria, Cladosporium, Penicillium) are not allergic to mold cheese. The
most important allergen in cheese is casein (f78).

Goat's milk
Goats milk often appears as a substitute for cow's milk, particularly in diets
administered by parents to children with atopic dermatitis (41). Many cow's
milk-allergic children tolerate goat's milk (13). However, there appears to
be evidence for crossreactivity between goat's milk and cow's milk (16). In
a study of crossreactivity of the casein fractions among different species,
the IgE response to ewe and goat's milk was weaker than that to cow and
buffalo(4).

Mare's milk
Cow's milk allergic patients using ointments containing mare's milk have
suffered severe clinical symptoms (23). Crossreactivity between cow's
milk and mare's milk has been shown in RAST inhibition (23). The authors
suggest the crossreactivity is linked to a sensitization to casein.

Whey

whey powder
Whey is the by-product of cheese-making. Whey is commonly included as
an ingredient in baked goods, bread, ice cream, frozen desserts, dry
mixes, processed cheese, confections, sauces and gravies. It is also a
substitute for non-fat dry milk in cream fillings. It is an additive in foods
which require dairy protein solids with a high balance of minerals including
meat products, cheese foods and seasoning mixes.
Milk proteins contain about 20% whey components. These are denatured
in varying degrees by heating (20). a lactalbumin, B-lactoglobulin and
bovine serum albumin (BSA) are major allergens of whey.

Clinical experience
Ellis et al. (13) reported anaphylaxis after ingestion of a hydrolyzed whey
protein formula in an infant. They urged caution when introducing such
formulae to highly sensitive children.

Editorial: Constipation in children

The New England Journal of Medicine;

Volume:
Issue:
Start Page:
ISSN:
Subject Terms:

Boston; Oct 15, 1998; Vera Loening-Baucke

339
16
1155-1156
00284793
Editorials
Children & youth
Digestive system
Milk
Proteins

Abstract:

An editorial addresses an article by Iacono et al, in which they provide further

evidence that intolerance of cow's-milk protein is a cause of chronic constipation in
children.

Full Text:
Copyright Massachusetts Medical Society, Publishing Division Oct 15,
1998

CONSTIPATION is a frequent problem among infants and children. For example, in a

U.S. study, 16 percent of parents of 22-month-olds reported that their children had
constipation.1 In the United Kingdom, 34 percent of 4-to-7-year-old children were said to
be constipated,2 and the frequency was 37 percent among 1005 Brazilian children who
ranged in age from birth to 12 years.3 Most often, constipation is short-lived and of little
consequence; however, chronic constipation does occur, as shown in the British study, in
which 5 percent of the children had constipation lasting for more than six months.2

Intolerance of cow's-milk protein occurs in 0.3 to 7.5 percent of otherwise normal

infants,4,5 82 percent of whom have symptoms within four months of birth and 89
percent by one year of age.6 This intolerance most often causes vomiting and diarrhea but
can also cause allergic rhinitis, asthma, and eczema. More recently, gastroesophageal
reflux and chronic constipation caused by anal erythema, anal fissures, anal fistulas, and
proctitis have been attributed to intolerance of cow's-milk protein.7-9 Intolerance of
cow'smilk protein is not a transient disorder; only 28 percent of infants with such
intolerance were unaffected by a challenge with cow's milk at the age of two years, 56
percent at four years, and 78 percent at six years.10
How strong is the evidence that intolerance of cow's milk causes constipation? An
international working group recommended that the elimination of a food from the diet
followed by challenge with the food is crucial in the diagnosis of food allergy with
predominantly gastrointestinal symptoms.11 In a study of 206 infants with intolerance of
cow's-milk protein, 6 percent had constipation that was unresponsive to a variety of
treatments: the addition of carbohydrates, juices, fruits, and malt to the diet, anal dilation,
and the administration of laxatives.6 In these children, normal bowel habits returned after
the complete withdrawal of cow's milk from the diet. In a study by Iacono et al. of 27
Italian children 5 to 36 months of age who had constipation, the constipation disappeared
in 78 percent during a trial of a cow's-milk-free diet and reappeared within 48 to 72 hours
after challenge with cow's milk.9 Therefore, the authors concluded that the constipation
was a symptom of intolerance of cow's milk.
In this issue of the Journal, Iacono et al.12 provide further evidence that intolerance of
cow's-milk protein is a cause of chronic constipation in children. They defined chronic
constipation as having one bowel movement every 3 to 15 days and, in many cases,
having abdominal symptoms as well. Many patients had anal fissures and perianal
erythema or edema. The investigators performed a double-blind, crossover study of cow's
milk as compared with soy milk in 65 children with constipation who were 11 to 72
months of age and had not had a response to previous laxative treatment. In 68 percent,
the number of bowel movements increased to eight or more over a 15-day period - the
definition of a response - when they were fed a cow's-milk-free diet.l2 Anal fissures and
pain on defecation resolved. None of the children had a response when they received
cow's milk.
How often is cow's-milk intolerance the cause of chronic constipation in children? It is
difficult to know, because most studies are from referral centers and are of children who
have not responded or have responded only partially to treatment prescribed by their
primary care physicians. Many children have been treated with laxatives for only a few
days at a time, often in inadequate doses, or have received stool softeners, the efficiency
of which has not been established. Many parents discontinue the laxative treatment for
fear that laxatives will be habit forming. In addition, over-the-counter laxatives are not
approved for children younger than two years of age except under the direction of a
physician.

At our tertiary care center, increasing the daily laxative dose has relieved constipation in
most children. My colleagues and I studied 174 children less than four years of age who
had chronic constipation.'3 Ninety-three percent had not had a response to treatment with
laxatives. Eight percent had blood in the stool at the time of the initial evaluation.
Treatment consisted of fecal disimpaction, prevention of future stool impaction,
promotion of regular bowel habits with dietary fiber and milk of magnesia, and finally,
toilet training of preschool children. Treatment recommendations for infants included the
addition of corn syrup to formula and feeding with pureed fruit and vegetables at a few
months of age. Milk of magnesia (1 to 2 ml per kilogram of body weight) was given if
dietary changes were unsuccessful. We were able to evaluate long-term outcome in 90 of
these children, a mean of seven years after the initial evaluation and treatment. Sixtythree percent had had a recovery, defined as no soiling and three or more bowel
movements per week, without further laxative treatment. Constipation had recurred in 34
percent as soon as laxatives were discontinued; 2 percent were unresponsive to treatment.
Recently we have suggested that children be switched from a regular cow's-milk-based or
soybean-- based formula to a protein-hydrolysate formula containing 100 percent whey
as the protein rather than prescribing laxatives, because few children receiving this
formula had constipation.l4 For a long time, we assumed that the casein in the cow's-milk
formula was the culprit; given the fact that the hydrolysis of whey, with a resulting
reduction in the antigenicity of the cow's-milk protein, led to the resolution of the
constipation, we are no longer sure that casein causes constipation.
The findings of Iacono et al. need confirmation at other centers, because much of the
published research has come from their group. Nonetheless, some children who do not
respond to treatment with laxatives, who have blood in the stool at the initial visit, or who
have the constellation of findings reported by Iacono et al. may have intolerance of
cow's-milk protein. For all children with constipation who do not have a response to
laxatives and an increase in dietary fiber, a trial of the elimination of cow's milk should
be considered.
[Reference]
REFERENCES

[Reference]
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abnormal dietary patterns? Diet and digestive complaints in children at 22 and 40 months of age. Am J Dis Child
1987;141:679-82. 2. Yong D, Beattie RM. Normal bowel habit and prevalence of constipation in primary school
children. Ambulatory Child Health (in press). 3. Zaslavsky C, Avila EL, Araujo MA, et al. Constipacao intestinal da
infancia - um estudo de prevalencia. Rev AMRIGS 1988;32:100-2. 4. Gerrard JW, MacKenzie JW, Goluboff N,
Garson JZ, Maningas CS. Cow's milk allergy: prevalence and manifestations in an unselected series of newborns.
Acta Paediatr Scand Suppl 1973;234:1-21. 5. Schrander JJ, van den Bogart JP Forget PP Schrander-Stumpel CT,
Kuijten RH, Kester AD. Cow's milk protein intolerance in infants under 1 year of age: a prospective
epidemiological study. Eur J Pediatr 1993;152: 640-4. 6. Clein NW Cow's milk allergy in infants. Pediatr Clin North
Am 1954; 4:949-62. 7. Cavataio F, Iacono G, Montalto G, et al. Gastroesophageal reflux associated with cow's
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KC, Tarlow MJ, Allfree AJ. Allergy to cows' milk presenting as chronic constipation. BMJ 1983;287:1593.

[Reference]
9. Iacono G, Carroccio A, Cavataio Fl Montalto G, Cantarero MD, Notarbartolo A. Chronic constipation as a
symptom of cow milk allergy. J Pediatr 1995;126:34-9. 10. Bishop JM, Hill DJ, Hosking CS. Natural history of cow
milk allergy: clinical outcome. J Pediatr 1990;116:862-7. 11. The European Society for Paediatric
Gastroenterology and Nutrition Working Group for the Diagnostic Criteria for Food Allergy. Diagnostic criteria for
food allergy with predominantly intestinal symptoms. J Pediatr Gastroenterol Nutr 1992;14:108-12. 12. Iacono G,
Cavataio F, Montalto G, et al. Intolerance of cow's milk and chronic constipation in children. N EngL J Med

1998;339:1100-4. 13. Loening-Baucke V. Constipation in early childhood: patient characteristics, treatment, and
longterm follow up. Gut 1993;34:1400-4. 14. Steffen R, Loening-Baucke V. Idiopathic constipation. Pediatrics (in
press).

[Author note]
VERA LOENING-BAUCKE, M.D. University of Iowa Iowa City, IA 52242