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COWS’ MILK PROTEIN ALLERGY (CMPA) OR COW MILK
PROTEIN INTOLERANCE( CMPI)

"...an adverse reaction to cows' milk resulting
from an
immunologic hypersensitivity to one or more
milk proteins“1
How many infants are affected?
 Most common food allergy in infancy

Affects an estimated 2-7.5% of UK births1
– 5% would be 38,000 babies/year
(imagine filling the 02 arena twice over)

Generally
by270-276.
1-3 years of age
1 Hill DJ et al. Jresolves
Pediatr 1986; 109;
2. Høst A. Ann Allergy Asthma Immunol 2002; 89 (6 Suppl 1): 33-37.
• Cow's milk proteins are most frequently implicated
as a cause of food intolerance during infancy.
• Soybean protein ranks second as an antigen in the
first months of life, particularly in infants with
primary cow's milk intolerance who are placed on a
soy formula. From school age on, egg protein
intolerance becomes more prevalent.
• Several clinical reactions to food proteins have been
reported in children and adults. Only a few of these
have a clear allergic immunoglobulin E (IgE)–
mediated pathogenesis.
• The term "food protein allergy " is usually preferred
to "food protein intolerance “.
ALLERGY VS INTOLERANCE
Hypersensitivity
Involving the
immune system
Food allergy
(allergic hypersensitivity)
IgE mediated allergy
Non-IgE mediated allergy
Adapted from Johansson SGO et al. 2004.
Not involving the
immune system
Food intolerance
(non-allergic hypersensitivity)
PATHOPHYSIOLOGY
• Cow's milk contains more than 20 protein fractions : 4 caseins ,S1, S2, S3, S4: 80%
of the milk proteins; 20% of the proteins globular proteins (eg, lactalbumin,
lactoglobulin, bovine serum albumin)
• Casein is often considered poorly immunogenic because of its flexible,
noncompact structure.
• Lactoglobulin is the major allergen in cow's milk protein intolerance.
• The proteins recognized by specific IgE are the lactoglobulin and the casein
fraction. However, all milk proteins appear to be potential allergens, even those
that are present in milk in trace amounts (eg, serum bovine albumin,
immunoglobulins, lactoferrin)
• In each allergen, numerous epitopes can be recognized by specific IgE presence.
Cow's milk proteins introduced with maternal diet can be transferred to the
human milk (presence of bovine lactoglobulin throughout human lactation)
• The GI tract is permeable to intact antigens. The antigen uptake is an endocytotic
process that involves intracellular lysosomes.
• Morphologic studies have demonstrated the role of GI T
lymphocytes (ie, intraepithelial lymphocytes) in the pathogenesis of
GI food allergy.
• Protein intolerance is generally believed to remit by age 5 years,
when the infant's mucosal immune system matures and the child
becomes immunologically tolerant of milk proteins;
•
In most affected children, symptoms resolve by age 1-2 years.
• Cow's milk protein intolerance may persist or may initially manifest
in older children (characteristic endoscopic and histopathologic
features);it occasionally recurs in adults.
EPIDEMIOLOGY
• Incidence of food allergy in children has been
variously estimated at 0.3-8%, and the
incidence decreases with age.
• Food allergies affect 6-8% of infants younger
than 2 years.
• Denmark : incidence of 2.2%
• the EuroPrevall-INCO project has been
developed to evaluate the prevalence of food
allergies in China, India, and Russia
CLINICS
Body system affected
Symptoms
Oral tract
• Itching and
redness
of mouth and lips
Respiratory tract
• Rhinitis
• Asthma
• Wheezing
Skin
• Urticaria
• Angiodema
• Atopic dermatitis
Gastrointestinal
tract
• Vomiting
• Abdominal pain
• Diarrhoea
CLINICS
• The typical history is that of an infant younger
than 6 months who is fed for a few weeks with
formula and who then develops diarrhea and,
eventually, vomiting;
• the infant can become dehydrated and lose
weight;
• cow's milk enteropathy (rare): malabsorption
syndrome develops, with growth failure and
hypoalbuminemia.
• Cow's milk proteins and soy proteins can cause
an uncommon syndrome of chronic diarrhea,
weight loss, and failure to thrive, similar to that
appearing in celiac disease. Vomiting is present in
up to two thirds of patients. Small bowel biopsy
findings reveal an enteropathy of variable
degrees with villous hypotrophy. Total mucosal
atrophy, histologically indistinguishable from
celiac disease, is a frequent finding. Intestinal
protein and blood losses can aggravate the
hypoalbuminemia and anemia that are frequently
observed in this syndrome.
CLINICS
• GI symptoms Oral allergy syndrome: Oral allergy
syndrome is a form of IgE-mediated contact allergy
that is almost exclusively confined to the
oropharynx and is most commonly associated with
the ingestion of various fresh fruits and vegetables.
Symptoms : itching; burning; and angioedema of
the lips, tongue, palate, and throat. The clinical
picture is usually short-lived, but symptoms may be
more prominent after the ragweed season.
• Eosinophilic esophagitis occurs in children and adults but
rarely occurs in infants and is characterized by chronic
esophagitis, with or without reflux.
• Children younger than 2 years often present with food
refusal, irritability, vomiting, and abdominal pain.
• In older children, dysphagia, anorexia, and early satiety can
help distinguish eosinophilic gastroenteritis
from gastroesophageal reflux
• Eosinophilic gastritis: Eosinophilic gastritis that is responsive
to elimination diets has occasionally been reported.
Symptoms: postprandial vomiting, abdominal pain, anorexia,
early satiety, and failure to thrive. Approximately half of these
patients have atopic features.
• Eosinophilic gastroenteritis: Symptoms include protracted
vomiting and diarrhea. Vomiting generally occurs 1-3 hours
after feeding, and diarrhea occurs 5-8 hours after feeding.
•
•
•
•
Blood in the stools
Chronic constipation
Infantile colic
Endoscopic finding of lymphonodular
hyperplasia
• Multiple food protein intolerance of infancy
Dermatologic symptoms
• urticaria, angioedema, rashes, and atopic
eczema.
• atopic dermatitis is one of the most common
symptoms of protein intolerance- 20-40% of
children younger than 1 year with protein
intolerance have atopic dermatitis. Most children
with atopic dermatitis and protein intolerance
develop a complete tolerance in a few years.
• Umbilical and periumbilical disappeares within
the second week on elimination diet, and
reappears within 24 hours after challenge
• Respiratory symptoms: rhinitis and asthma.
General symptoms
• Nonspecific symptoms: oral aphthae, pyloric stenosis,
and bowel edema and obstruction
• The infant with enterocolitis syndrome can be
dehydrated as a consequence of diarrhea, vomiting, or
both. Signs of dehydration include blunted eyes, dry
mucous membranes, and hypoelastic skin.
• Dystrophy, growth failure, edema (hypoalbuminemia),
rickets (vitamin D malabsorption), and hemorrhages
(vitamin K malabsorption)
•
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Differential Diagnoses
Crohn Disease
Gastroenteritis
Gastroesophageal Reflux
Ulcerative Colitis
Celiac disease
Lactose intolerance
Prolonged post-enteritis syndrome
Autoimmune enteropathy
Common variable immunodeficiency
Food allergy
Infections (Giardia, Helicobacter, Cryptosporidium, viruses)
Food allergy
Drug reactions (NSAIDS, chemotherapy)
Immune system abnormalities (GVHD, autoimmune enteropathy,
other autoimmune diseases)
Laboratory Studies
• Skin test responses to cow's milk or other food proteins and
detection of food-specific immunoglobulin E (IgE) antibodies
are usually positive in children with IgE-mediated food allergy.
• Serum immunoassays: Serum immunoassays to determine
food-specific IgE antibodies are often used to screen for
antigen-specific IgE in the patient's serum. Enzyme-linked
immunosorbent assays (ELISAs) have been replacing methods
that use radiation (eg, radioallergosorbent test [RAST]).
• Fecal leukocyte testing: Fecal eosinophils are a significant clue
to the diagnosis of allergic colitis.
• Atopy patch testing:
• Elimination diets: elimination of suspected food antigens from
the diet for 2-4 weeks or longer. An elimination diet for 10-14
days should precede a food challenge test.
• Total serum IgE is within the reference range or slightly
elevated.
Upper GI and lower( colonoscopy) endoscopies :
• hyperemia of the mucosa, rings, and plaques
• focal erythema and frequent nodularity
• eosinophilic infiltration, most prominent in
the lamina propria, can be observed in the
biopsy specimens
TREATMENT
• The definitive treatment of food protein
intolerance is strict elimination of the offending
food from the diet
• dietary therapy of 3 possible regimens: strict use
of amino acid–based formula, dietary restriction
based on allergy testing, or dietary restriction
based on eliminating the most likely food
antigens. The committee also recommended that
topical steroids should be considered for both
initial and maintenance therapy ( 2011)
• Topical or orally and intranasally inhaled
corticosteroids are used to treat dermatologic or
respiratory symptoms (Triamcinolone topical ,
Hydrocortisone topical )
• Antihistamines and inhaled
bronchodilatators (Beclomethasone)
• Infants with elevated cord serum immunoglobulin E
(IgE) and a positive family history of atopy are at
risk for the development of atopic disease.
• In some infants at high risk, exclusive breastfeeding
with delayed introduction of solid foods until the
infant is aged 6 months may delay or possibly
prevent the onset of food allergy.
• avoidance of allergenic foods by lactating mothers
• The American Academy of Pediatrics (AAP): avoid eggs
until age 2 years; peanuts, tree nuts, and fish until age
3 years for infants who are at risk of developing atopic
disease.
• The Committee on Nutrition and Section on Allergy and
Immunology of the AAP states that this raises serious
questions about the benefit of delaying the
introduction of solid foods that are thought to be highly
allergic beyond age 4-6 months
• The intestinal microflora interacts with the mucosal
immune system, and, in germ-free mice, does not
develop a normal oral tolerance. The intestinal flora of
children with atopy has been found to differ from that
of controls. These observations suggest that the normal
flora can play a role in the prevention of food allergies.
• A potential role for probiotics can be hypothesized
(Lactobacillus rhamnosus)
MANAGEMENT IN BREAST FED INFANTS
MILD TO MODERATE:
1. CONTINUE BREAST FEEDING BUT ELIMINATION IN MOTHER ‘
DIET 2-4 WEEKS WITH CA SUPPLEMENT AND NO EGG
2. IF IMPROVEMENT REINTRODUCE CMP AND CHECK SYMPTOMS –
IF YES THEN eHF AFTER BF, SOLIDS WITHOUT CMP UNTIL 9-12
MONTHS AND AT LEAST FOR 6/12. EGG TO BE ADDED IF NO
SYMPTOMS.
SEVERE CMPA:
1. REFER PAEDIATRICS AND IN MEANTIME ELIMINATION DIET IN
MOTHER PLUS CA SUPPLEMENT
Breastfeeding is the gold standard
in infant nutrition to 6 months
Protection
against
Protection
chest
against
infections
diarrhoea and
and
upset
wheezing
stomach
Lower risk
of
Less
smelly diabetes
nappies
Less
eczema
Protectio
n against
ear
infections
Breastmilk content per 100ml1
Better
mental
development
• Soya-based formulas -historically used for the management of
food hypersensitivity (e.g. lactose intolerance and CMPA)
• However, studies have shown that some 30-50% of infants
given a soya-based formula for the management of CMPA
present with concomitant soya protein allergy
• Soya-based formulas should not be first choice for the
management of infants with proven cows’ milk sensitivity due
to the potential risk from their high phytoestrogen levels
• Soya-based formulas should only be used in exceptional
circumstances to ensure adequate nutrition, e.g. for vegans or
infants who find alternatives unacceptable
• ESPGHAN are also in agreement and state that "Soya protein
formula should not be used in infants with allergy during the
first 6 months of life”. They also raise concerns over their use
post 6 months and suggest that soya tolerance "should first
be established by clinical challenge”2
Prescribable indications
Product
Indications
Uses
Cows’ milk protein intolerance
± secondary lactose intolerance
Cows’ milk protein
allergy/intolerance
Disaccharide ± whole protein
intolerance, or where amino acids
and peptides are indicated
for use with MCT
Complex multiple food
intolerances and malabsorption
Disaccharide ± whole protein
intolerance
Cows’ milk protein allergy
Cows' milk allergy, multiple food
protein intolerance and other
conditions where
an elemental diet is indicated
Severe cows’ milk allergy
and multiple food intolerances
CONCLUSION
• CONSIDER CMPA EARLY- REMEMBER GOR IS
AS COMMON AND DOES NOT NEED
ELIMINATION DIET
• TREAT EARLY
• AVOID SOY BASED FORMULAE UNTIL AT LEAST
6 MONTHS. AVOID GOAT’S MILK, RICE MILK
(ARSENIC) AS NOT APPROPRIATE CALORIES
AND NUTRITION
• IF IN DOUBT DISCUSS WITH COLLEAGUES