Cow's milk protein allergy (CMPA) is the leading cause of food allergy in infants and young children, affecting approximately 5-15% of infants. Breastfeeding reduces the risk of CMPA to around 0.5% compared to formula-fed infants who have a higher risk. CMPA results from an immune reaction to proteins in cow's milk and can cause symptoms in the gastrointestinal, skin, and respiratory systems. Diagnosis involves an elimination diet and oral food challenge. Extensively hydrolyzed formulas are recommended for mild-moderate CMPA, while amino acid-based formulas are used for severe cases.

1. COW MILK PROTIEN ALLERGY

2. INTRODUCTON
Adverse reaction to food divided to :
• Food intolerance : physiological response like;
lactose intolerance, IBS,IBD ..
• Food allergy :
Food allergy defined as adverse health affection
from a specific immune response that occurs
following exposure to antigenic food component
The immune reaction may be immunoglobulin
(IG)E mediated, non IGE mediated, or mixed

3. Epidemiology
Cow`s milk protein (CMP) is the leading cause
of food allergy in infants and young children.
Infants show symptoms suggesting adverse
reactions to cow's milk protein (CMP)about 5%
and 15% .
while appropriate diagnosis only 2-3% are
CMPA.
After 6years falls to less 1%.
N.B: Cross reactive with (goat`s **, sheep`s,
buffalo not mare`s milk)

4. Other high risk foods to allergy include:
• Hen`s egg white ( 1.5%) early
presentation but resolves 7 years old
• Peanut ( 1%)2 years old and persists
• Fish ( late childhood and persists)
• Wheat and gluten containing food (RBW;
rye, barley, wheat) 6m – 24 m

5. The incidence of CMPA is lower in exclusively
breast-fed infants (only about 0.5%)compared to
formula-fed or mixed-fed infants.
1) This might be related to the fact that the level of
CMP present in breast milk is 100 000 times
lower than that in cow’s milk
2) Immunomodulators present in breast milk
3) differences in the gut flora in breast-fed and
formula-fed infants may contribute to the
prevalence of CMPA in breast-fed compared to
formula-fed.

6. Prevention guidelines*
• Exclusive breastfeeding has been shown to be
the best method to prevent allergy
• Recent guidelines are consistent in their
recommendation that maternal diet should not
be modified during pregnancy or lactation as a
strategy for preventing the development or
clinical course of food allergy
• Introduce complementary solid food at (4-6
months); first low risk then high risk foods

7. guidelines routinely recommend the use of hydrolyzed
formulae (not soy based) for the prevention of CMPA
in infants with an increased risk of allergy based on family
history of atopic disease

8. RISK FACTORS OF ALLERGIC
DISEASES
Both parents are atopic have 50 % child
allergic.
One parent equals risk of 20 %
Neither is atopic equals 10 % risk.

9. pathophysiology
CMPA results from an immunological
reaction to one or more milk proteins.
This immunological basis distinguishes
CMP allergy from other adverse reactions to
CMP which called food intolerance such as
lactose intolerance (mostly physiological
mechanism )

10. IgE antibodies bind mast cells, basophils and
macrophage to fc receptor.
When allergens penetrates mucosa activate
these cells and release mediators causing
vasodilatation and secretions. Lead to
acute allergic manifestations
IgE mediated

11. • skin ( urticaria, angioedema, flushing)
• GIT ( pruritus, abdominal pain, vomiting, diarrhea).
• Respiratory (nasal congestion, wheezing,
rhinorrhea)
• cardiovascular ( hypotension , loss of
consciousness)

13. Food allergen specific T cells release
cytokines the lead to delayed inflammatory
process
Skin (erythema)
GIT (failure to thrive, vomiting, diarrhea)
Respiratory (pulmonary hemosidrosis)
Non IgE MEDIATED

14. Mixed pathology
Chronic disorders such as ;
(Atopic dermatitis, asthma, allergic eosinophilic
esophagitis, gastroenteritis)

15. Formula
Allergenicity decreasre with decresing chain
length

16. • Two mechanisms

17. Clinical presentation
Unfortunately, there is not one symptom that
is pathognomonic for CMPA
As any type of allergy Many children with
CMPA develop symptoms in at least two of
organ systems

18. gastrointestinal (50–60%)
Frequent regurgitation
Vomiting
Diarrhoea
Constipation (with/without perianal
rash)
Blood in stool
Iron deficiency anaemia

19. Skin (50–60%)
• Atopic dermatitis
• Swelling of lips or eye lids (angio-oedema)
• Urticaria unrelated to acute infections,
drug intake or other causes

20. Respiratory tract (20–30%).
• Runny nose or (recurrent otitis media)
• Chronic cough (unrelated to infection)
• Wheezing

21. General
Persistent distress or colic (irritable for ⩾3 h
per day) at least 3 days/week over a period
of >3 weeks

23. severe CMPA as the possible cause
Gastrointestinal tract
Failure to thrive due to chronic diarrhoea or refusal to feed or vomiting
Iron deficiency anaemia due to occult or macroscopic blood loss
Hypoalbuminaemia
Endoscopic/histologically confirmed enteropathy or severe colitis
Skin
Exudative or severe atopic dermatitis
Respiratory tract
Acute laryngoedema
bronchial obstruction with difficulty breathing(unrelated to infection)
General
Anaphylaxis

24. Differential diagnoses
• metabolic disorders
• anatomical abnormalities
• coeliac disease and other (rare) enteropathies,
pancreatic insufficiency (such as in cystic fibrosis),
non-immunological adverse reactions to food (such
as fructose malabsorption or secondary lactose
intolerance,
• allergic reactions to other food allergens (such as
hen’s eggs, soy, wheat, etc) or other substances
(such as animal dander, moulds, dust),
• infections (particularly gastrointestinal and urinary
tract infections) and sepsis

25. Diagnosis and elimination
Differ in breast feeding from formula fed infants.
• The elimination diet should be continued for a
minimum of at least 2 weeks, and up to 4
weeks in cases of atopic dermatitis or allergic
colitis.
• The mother will require calcium supplements
(1000 mg per day divided into several doses)
during the elimination diet.

27. Diet of mother
maternal exclusion diet avoiding food
containing CMP and hen’s eggs.
subgroup of children with severe atopic
dermatitis peanut eliminated from the
mother’s diet
a diet that also excludes fish, wheat and
other gluten-containing grain products is very
demanding for the mother and may increase
the mother’s risk of consuming an
unbalanced diet

28. the elimination diet should be adapted
accordingly if suspicion of another food
In some very rare cases, such as in infants
with severe atopic dermatitis with impaired
growth, breast feeding should be stopped

31. If symptoms improve substantially or
disappear during the elimination diet,
one food per week can be reintroduced to the
mother’s diet. If symptoms do not re-appear
on reintroduction of a particular food to the
mother’s diet, the elimination of that specific
food can be discontinued.

32. Formula fed infants
mild-to-moderate CMPA symptoms
• CMP elimination should start with a therapeutic formula for
CMPA.
• The guidelines define a therapeutic formula as one that is
tolerated by at least 90 % of CMPA infants
• They are extesively hydrolysed formula (90%)
• and amino acid-based formula (100%)
Severe CMPA symptoms
recommended to start with amino acid-based
formula because infants in this group fail to thrive, suffer from
macronutrient deficiencies or life threatening.

33. • supplementary food should be stopped
during the diagnostic elimination diet.
• After 6months the diet should not contain
CMP or hen’s eggs, soy protein or peanut.
• If no improvement, further elimination of
other allergenic proteins such as fish and
wheat may be appropriate.
• If symptoms do not disappear on the AAF,
another diagnosis should be considered.

34. What about soy based formula
• Although soy formulations are significantly
cheaper and have a better acceptance than
eHF and AAF
1. soy formulations contain high concentration
of phytate, aluminium and phyto-
oestrogens
2. Adverse reactions to soy have been
reported in 10–35% of infants with CMPA,
regardless of whether or not they were
positive or negative for specific IgE
antibodies for CM

35. • Partially hydrolyzed formulae based on
CMP
• other mammalian protein are not
recommended for infants with CMPA

36. Challenge test
• After documentation of significant improvement on the
• diagnostic elimination, the diagnosis of CMPA should be
confirmed
• by a standardized oral challenge test
• documentation of any signs and symptoms and the milk
volume that provokes symptoms
• Type of Milk and Dose
• In the first year of life, a challenge test should be performed
with an infant formula based on cow’s milk. Fresh pasteurized
cow’s milk can be used above 12 months of age
• in children older than about 3 years the challenge procedure
may be performed with lactose-free CMP-containing milk

37. • The starting dose during an oral milk challenge should
be lower than a dose that can induce a reaction and
then be increased stepwise to 100 mL (eg, in children
with a delayed reaction, stepwise doses of 1, 3.0, 10.0,
30.0, and 100 mL may be given at 30-minute intervals
• If severe reactions are expected, then the challenge
should begin with minimal volumes (eg, stepwise
dosing of 0.1, 0.3, 1.0, 3.0, 10.0, 30.0, and 100 mL
given at 30-minute intervals).
• If no reaction occurs, then the milk should be
continued at home every day with at least 200 mL/day
for at least 2 weeks. The parents should be contacted
by telephone to document any late reactions.

38. Role of investigations
None of the available diagnostic tests prove or disprove
that the child suffers from CMPA.
Serum specific IgE: sensitivity 87 % and specificity 48 %.
Skin prick test: sensitivity 88 % and specificity 68 %
Mostly needed for multiple food allergy
it is preferable to test for specific IgE (if not performed
during the diagnostic work‐up) in children with CMPA
proven on challenge. helpful in predicting the prognosis
and interval until the next challenge.

39. If these infants have a SPT with a reaction with
a large diameter (>7 mm) or very high titres in
the IgE test the confirmatory CMP challenge
can be postponed until the child shows a
reduced reaction in the tests for CMP-specific
IgE and challenge under medical supervision

40. • The concentration of calprotectin increases in
infection, inflammation, and malignancy.
• statistically significant difference FC values
before and after CMP elimination diet in non-
IgE-mediated groups.
• But IgE-mediated not significant
• FC levels may be a useful marker for follow-up
treatment and recurrence determination in
CMPA.
Can Fecal Calprotectin Level Be Used as a Markers
of Inflammation in the Diagnosis and Follow-Up of
Cow's Milk Protein Allergy?

42. reevaluation
The duration of exclusion will depend on the age, severity of a
child’s symptoms, and positivity of specific
IgE for CMP.
therapeutic diet maitained for at least 3 months(eg, specific IgE
negative, mild symptoms) up to at least 12months(eg, high-
positive IgE test or severe reaction).
• If a challenge is positive, then the
elimination diet is usually continued for between 6 and 12 months.
• If the challenge is negative, then cow’s milk is fully reintroduced
into the child’s diet.

43. prognosis
CMPA persists in only a minority of children
Prognosis depends on the patient's age and titre
of specific IgE at the time of diagnosis
IGE negative become tolerant to CMP much
earlier than atopic children with positive test
results.
IgE‐positive CMPA are at increased risk of
developing atopic diseases, such as asthma,
atopic dermatitis and rhinoconjunctivitis, than
those who were IgE‐negative.

44. • Children with negative tests are less likely
to develop multiple food allergy
• it is preferable to test for specific IgE (if not
performed during the diagnostic work‐up)
in children with CMPA proven on
challenge.