Cow`s Milk Protein Allergy

Muzal Kadim
Division of Gastrohepatology, Child Health Department
Faculty of Medicine University of Indonesia
 Introduction
Breastfeeding
Symptoms
Prevention
Treatment
 Adverse reaction to food

Food intolerance Pseudo

Psycho
Inborn error Food allergy Allergic
of metabolism pathological
reaction

GI IgE/TH2 Non IgE

Systemic Food additive
e.g.Lactose mediated mediated
e.g. PKU intolerance Histamine

Systemic
e.g. Atopic CMPSE
Colic
 Adverse reaction to food…
Immunologic Spectrum
IgE-Mediated Non-IgE Mediated

• Oral Allergy • Eosinophilic esophagitis • Protein-Induced

Syndrome • Eosinophilic gastritis Enterocolitis
• Anaphylaxis • Eosinophilic • Protein-Induced
• Urticaria gastroenteritis Enteropathy
• Atopic dermatitis • Eosinophilic proctitis
Food hypersensitivity among Caucasian and non
Caucasian children
Dias RP. Pediatr allergy Immunol.2008;19:6-9

Population Non-Caucasian
- General pediatric clinic 35.9%
- Pediatric allergy clinic 52.6%

Caucasian Non-Caucasian
No food allergen/child 2.25 1.22
Age first reaction (yr) 1.7 2.6

125 reaction in the study population

- Top 5 (egg, peanut, tree nut, cow milk and cod)
- Novel food (kiwi, lentil, sesame particularly non Caucasian)
 Contact with food allergen

Gastrointestinal tract
-The largest organ
-Continuously contact with
substances
-Foreign to the human being
-Barrier between outside and 4 m2 40 m2
internal side
-Mechanical and functional
-Immunologic and non immunologic
-Intraluminal digestion/absorption
-Major contact allergen

400 m2
 Contact with food allergen…

Inhallation of food protein, skin contact

Jarmoc LM. Clin Pediatr Phila 1987;26:154-5
Bahna SL. Allergi 1994;19:129-30
Igea JM. J allergy Clin Immunol 1994;94:33-5
Anto JM.N England J Med 1993;329:1760-3
Bosetti M. Allergy 1997;52(Suppl 37):121A

CMP detected in large amounts in house dust

Witteman AM. Int Arch Allergy Immunol 1995;107:566-8
Neonatal cow milk sensitization in 143 case reports:
role of early exposure to cow`s milk formula
Cantani A. Eur Rev Med Pharmacol Sci 2005;9(4):227-30

- The baby were probably sensitized

during the first day of life
- Particularly sensitizing appears to be
the exposure to CM formulas in the
neonatal nursery
 Interrelationship between Gastroentiritis, immune
deficiency And food-sensitive enteropathy
Walker-Smith and Murch 1997
Dilayed maturation Acute Gastroenteritis
of immune system

Constitutive
Mucosal IgA
immune
deficiency
dysregulation

Mucosal IgG Damage to Secondary

excess small intestinal Lactase
mucosa deficiency

Excess direct Secondary

antigen entry into Lactose
mucosa via intolerance
damage enterocyte

Oral Systemic Food-sensitive

tolerance sensitization enteropathy
abrogaded
 Introduction
Breastfeeding
Symptoms
Prevention
Treatment
 Breast feeding
↓ Incidence

- CMPA
- Acute otitis media
- Acute diarrhea
- Obesity
- Hypertension
- Atopic dermatitis
 Prevalence of CMPA

- 0,5% of breast feed infant

Host A. Pediatr Allergy Immunol 1994;5(Suppl);5-36
Saarinen K. J Pediatr Gastroenterol Nutr 1997;24:461

- 2% - 5% of formula feed
Vandenplas Y. Curr Opin Pediatr 1993;5:567-72
 Introduction
Breastfeeding
Symptoms
Prevention
Treatment
 Most frequent symptoms of CMPA
Vandenplas Y. Arch Dis Child 2007;92:902-8

- Gastrointestinal tract 50% - 60%

- Skin 50% - 60%
- Respiratory tract 20% - 30%
Most frequent symptoms of CMPA…
Symptoms following cow milk challenge
Hill DJ. J Peditr 1986; 109:270-6
Most frequent symptoms of CMPA…
Organ involvement Symptoms
Gastrointestinal tract Frequent regurgitation
Vomiting
Diarrhea
Constipation
Blood in stool
Iron deficiency anaemia
Skin Atopic dermatitis
Angio-oedema
Urticaria
Respiratory tract Runny nose (otitis media)
Chronic cough
Wheezing
General Persistent distress or colic
 Alarm symptoms for severe CMPA
Organ involvement Symptoms and findings
Gastrointestinal tract FTT due to chronic diarrhea and/or
refusal to feed and/or vomiting
Iron deficiency anemia due to occult
or macroscopic blood loss
Hypoalbuminemia
Endoscopic/histologically confirmed
enteropathy or severe colitis
Skin Exudative or severe atopic
dermatitis with hypoalbuminemia
or FTT or iron deficiency anemia
Respiratory tract Acute laryngoedema or bronchial
General Anaphylaxis
 GER and CMPA
Salvatore S, Vandenplas Y. Pediatrics 2002;110:972-84

- 15% - 21% of children with GERD or CMPA

suffer for both condition

- 16% - 42% of children with a history of

GERD have symptoms of CMPA
Asthma, allergic rhinitis, eczema and CMPA

asthma, allergic rhinitis and eczema

are more common in children
with history of CMPA
than would be expected
in the general population
Status of children with cow`s milk allergy in infancy by 10 years of age
Tikkamen S. Acta Paediatr 2000;89:1174-80

The natural history of food allergy

Wood RA. Pediatrics 2003;111(Supplement):1631-7
 Introduction
Breastfeeding
Symptoms
Prevention
Treatment
Meta-analysis of partial hydrolysed (pHF) formula
vs regular formula on primary allergy prevention
The effect of hydrolysed cow`s milk formula for allergy
prevention in the 1 st year of life: the GINI-study
Von berg A. J Allergy Clin Immunol 2003;111:533-40

Whey pHF Cas eHF Reguler Formula Breastmilk

 Formula containing hydrolysed protein for
prevention of allergy and food intolerance in infant
Osborn DA, Sinn J. Cochrane Database Syst Rev 2006

- No evidence to support feeding with a

hydrolysed formula for the prevention of
allergy compare to exclusive breast feeding

- In high risk infant who are unable to be

completely breast feed there limited
evidence that prolonged feeding with a
hydrolysed formula reduced infant and
childhood allergy
A specific mixture of short chain GOS and long chain
FOS induces a beneficial immunoglobulin profile in
infant at high risk for allergy
Van Hoffen E. Allergy 2008

• GOS/FOS supplementation induces a beneficial

antibody profile
• GOS/FOS reduces the total Ig response and
modulate the immune response toward CMP
• This suggest that oral GOS/FOS
supplementation is a safe method to restrain
the atopic march
Meta-analysis of clinical trials of probiotics for prevention
and treatment of pediatrics atopic dermatitis
Lee J. Allergy Clin Immunology 2008;121:116-21

21 trials (N = 1898, 0 – 13 years)

- 6 prevention trials some efficacy
- 4 treatment trials no efficacy
 Probiotics in infants for prevention of
allergic disease and food hypersenstivity
Osborn DA. Cochrane Database Syst Rev 2007

There is insufficient evidence to

recommend the addition of probiotics to
infant feeds for prevention of
allergic disease and food hypersenstivity
Age at first introduction of cow milk products and other food
products in relation to infant atopic manifestations in the
first 2 years of life: The KOALA Birth Cohort Study
Snijders BE. Pediatrics 2008;122(1):e115-22

2558 infants (0- 24 months)

- More delayed introduction of cow milk
products was associated with a higher risk
for eczema
- Delayed introduction of other food products
was associated with an increased risk for
atopy development at the age of 2 years
 Complementary feeding:
a commentary by ESPGHAN Committee onNutrition
Agostoni C. ESPGHAN Committee on Nutrition.
J Pediatr Gastroenterol Nutr 2008;46:99-110

There is no convincing scientific evidence

that avoidance or delayed introduction of
potentially allergenic food such us
eggs and fish reduced allergies
 Introduction
Breastfeeding
Symptoms
Prevention
Treatment
 Tata laksana
alergi susu sapi pada bayi
dengan ASI Eksklusif
dan bayi dengan susu formula

Rekomendasi
Ikatan Dokter Anak Indonesia (IDAI)
Diagnosis dan tata laksana alergi susu sapi
 Algorithm
for the Diagnosis and Management
of Cow’s Milk Protein Allergy (CMPA)
in exclusively Breastfed Infants

Vandenplas Y. Arch Dis Child 2007;92:902-8

 SUSPICION OF COW’S MILK PROTEIN ALLERGY

CLINICAL ASSESSMENT
Clinical findings
Family history (risk factor)

MILD / MODERATE SUSPICION OF SEVERE CMPA:

CMPA •Gastrointestinal: FTT (diarrhea or
regurgitation/ vomiting, refusal to feed,
moderate to large amounts of blood in stool
with  Hb, protein losing enteropathy)
• Dermatological: FTT and severe atopic
dermatitis
 SUSPICION OF COW’S MILK PROTEIN ALLERGY

CLINICAL ASSESSMENT

MILD / MODERATE SEVERE CMPA

CMPA

Referral to pediatric specialist

for diagnosis and treatment and
in the mean time elimination
diet in mother (no CMP, egg,
peanuts) and Ca-supplement
 SUSPICION OF COW’S MILK PROTEIN ALLERGY

CLINICAL ASSESSMENT
Clinical findings
Family history (risk factor)

SUSPICION OF MILD TO MODERATE CMPA:

One or more of the following symptoms:
 Gastrointestinal: frequent regurgitation, diarrhea, blood
in stool without failure to thrive or decreased
hemoglobin
 Dermatological: atopic dermatitis
 General: persistent distress, colic (> 3 hrs per day
wailing/irritable) over a period of > 3 weeks
 Others
 SUSPICION OF COW’S MILK PROTEIN ALLERGY

CLINICAL ASSESSMENT

MILD / MODERATE
CMPA

Continue BF
Elimination diet in mother No CM-
IMPROVEMENT
protein, egg, peanut for 2 weeks plus
Ca-supplement

NO IMPROVEMENT
(*) : breastfeeding can be continued,
Resume normal diet in mother and
topical treatment in case of atopic
consider other diagnosis (*)
dermatitis
 MILD / MODERATE CMPA

Continue BF
Elimination diet in mother
No CM-protein, egg, peanut for 2 weeks
Plus Ca-supplement

NO IMPROVEMENT IMPROVEMENT

Resume normal diet in mother

And consider other diagnosis REINTRODUCTION
One food / week in mother’s diet

SYMPTOMS NO SYMPTOMS
Maintain elimination diet resume normal diet in
in mother (+ Ca-suppl) mother and monitor

eHF after BF
solid foods free of CMP/egg;
challenge infant > 1 year
 Algorithm
for the Diagnosis and Management
of Cow’s Milk Protein Allergy (CMPA)
in Formula-Fed Infants

Vandenplas Y. Arch Dis Child.2007;92:902-8

 SUSPICION OF COW’S MILK PROTEIN ALLERGY

CLINICAL ASSESSMENT
Clinical findings
Family history (risk factor)

Testing for CMPA

Suspicion of Suspicion of
mild/moderate CMPA Consider the following severe CMPA
Skin tests: prick-test,
patch-test for CMP
Blood: Total IgE, specific
IgE (RAST) for CMP
 SUSPICION OF COW’S MILK PROTEIN ALLERGY
CLINICAL ASSESSMENT

Suspicion of Suspicion of
mild/moderate CMPA severe CMPA

ELIMINATION DIET (*) : Amino Acid Formula (AAF)

Clinically tested Depending on cost/benefit ratio
Extensively Hydrolysed Formula and/or
(eHF) for 2 to 4 weeks (*) if the child refuses to drink eHF

IMPROVEMENT NO IMPROVEMENT
 SUSPICION OF COW’S MILK PROTEIN ALLERGY
CLINICAL ASSESSMENT

Suspicion of Suspicion of
mild/moderate CMPA severe CMPA

ELIMINATION eHF 2 - 4 weeks (*)

IMPROVEMENT NO IMPROVEMENT

(#) preferable to do spec IgE CMP (RAST)

OPEN CHALLENGE (#) •> class 1 : no challenge (without iv line)
•< class 1 : challenge without iv line acceptable
cow’s milk formula and/or skin prick test
Clinical observation •SPT pos : no challenge (without iv line)
•SPT neg : challenge without iv line acceptable
 SUSPICION OF COW’S MILK PROTEIN ALLERGY
CLINICAL ASSESSMENT

Suspicion of Suspicion of
mild/moderate CMPA severe CMPA

ELIMINATION eHF 2 - 4 weeks (*)

IMPROVEMENT NO IMPROVEMENT

OPEN CHALLENGE (#)

cow’s milk formula
Clinical observation
CMPA SYMPTOMS
NO CMPA SYMPTOMS Maintain CMP REPEAT
resume CMP in diet elimination diet CHALLENGE
and monitor until age 9 - 12 months
for at least 6 months
 SUSPICION OF COW’S MILK PROTEIN ALLERGY
CLINICAL ASSESSMENT

Suspicion of Suspicion of
mild/moderate CMPA severe CMPA

ELIMINATION eHF 2 - 4 weeks (*)

IMPROVEMENT NO IMPROVEMENT

Consider
elimination diet with AAF
or
other diagnosis
and resume CMP in diet
 SUSPICION OF COW’S MILK PROTEIN ALLERGY

CLINICAL ASSESSMENT

Suspicion of Testing for CMPA Suspicion of

mild/moderate CMPA severe CMPA

REFERRAL TO
ELIMINATION DIET
and PEDIATRIC
Amino Acid Formula (AAF) SPECIALIST
minimal for 2 - 4 weeks

NO IMPROVEMENT IMPROVEMENT

Pediatric specialist Pediatric specialist

Diagnostic procedures challenge