Cow`s Milk Protein Allergy

Muzal Kadim
Division of Gastrohepatology, Child Health Department
Faculty of Medicine University of Indonesia


Introduction
Breastfeeding
Symptoms
Prevention
Treatment
Food intolerance
Inborn error
of metabolism
Pseudo
Allergic
reaction
Psycho
pathological
IgE/TH2
mediated
Food allergy
Adverse reaction to food
Food additive
Histamine
Non IgE
mediated
CMPSE
Systemic
e.g. Atopic
Colic
Systemic
e.g. PKU
GI
e.g.Lactose
intolerance
Eosinophilic esophagitis
Eosinophilic gastritis
Eosinophilic
gastroenteritis
Atopic dermatitis
IgE-Mediated
Non-IgE Mediated
Immunologic Spectrum
Oral Allergy
Syndrome
Anaphylaxis
Urticaria
Protein-Induced
Enterocolitis
Protein-Induced
Enteropathy
Eosinophilic proctitis
Adverse reaction to food
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
internal side
- Mechanical and functional
- Immunologic and non immunologic
- Intraluminal digestion/absorption
- Major contact allergen






4 m
2
40 m
2
400 m
2
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



Contact with food allergen


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



Constitutive
immune
dysregulation
Dilayed maturation
of immune system
Mucosal IgA
deficiency
Mucosal IgG
excess
Oral
tolerance
abrogaded
Acute Gastroenteritis
Damage to
small intestinal
mucosa
Excess direct
antigen entry into
mucosa via
damage enterocyte
Systemic
sensitization
Secondary
Lactase
deficiency
Secondary
Lactose
intolerance
Food-sensitive
enteropathy
Interrelationship between Gastroentiritis, immune
deficiency And food-sensitive enteropathy
Walker-Smith and Murch 1997
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%


0
10
20
30
40
50
60
70
80
90
100
Cutaneus Respir Gastro Gastro only
Clein
Goldman
Gerrad
Buisseret
Stinfzing
Most frequent symptoms of CMPA
Symptoms following cow milk challenge
Hill DJ. J Peditr 1986; 109:270-6
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

Most frequent symptoms of 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
Alarm symptoms for severe CMPA
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



CMPA
GERD Colic
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 Cows Milk Protein Allergy (CMPA)
in exclusively Breastfed Infants
Vandenplas Y. Arch Dis Child 2007;92:902-8
SUSPICION OF COWS MILK PROTEIN ALLERGY

CLINICAL ASSESSMENT
Clinical findings
Family history (risk factor)
MILD / MODERATE
CMPA

SUSPICION OF SEVERE 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 COWS MILK PROTEIN ALLERGY

CLINICAL ASSESSMENT

MILD / MODERATE
CMPA

SEVERE 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 COWS 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 COWS MILK PROTEIN ALLERGY

CLINICAL ASSESSMENT

MILD / MODERATE
CMPA

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

IMPROVEMENT
NO IMPROVEMENT
Resume normal diet in mother and
consider other diagnosis (*)
(*) : breastfeeding can be continued,
topical treatment in case of atopic
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 mothers diet
eHF after BF
solid foods free of CMP/egg;
challenge infant > 1 year
SYMPTOMS
Maintain elimination diet
in mother (+ Ca-suppl)
NO SYMPTOMS
resume normal diet in
mother and monitor
Algorithm
for the Diagnosis and Management
of Cows Milk Protein Allergy (CMPA)
in Formula-Fed Infants
Vandenplas Y. Arch Dis Child.2007;92:902-8
Suspicion of
mild/moderate CMPA
Suspicion of
severe CMPA
Testing for CMPA
Consider the following
Skin tests: prick-test,
patch-test for CMP
Blood: Total IgE, specific
IgE (RAST) for CMP
SUSPICION OF COWS MILK PROTEIN ALLERGY

CLINICAL ASSESSMENT
Clinical findings
Family history (risk factor)
Suspicion of
mild/moderate CMPA

Suspicion of
severe CMPA
ELIMINATION DIET
Clinically tested
Extensively Hydrolysed Formula
(eHF) for 2 to 4 weeks (*)
(*) : Amino Acid Formula (AAF)
Depending on cost/benefit ratio
and/or
if the child refuses to drink eHF
IMPROVEMENT
NO IMPROVEMENT
SUSPICION OF COWS MILK PROTEIN ALLERGY

CLINICAL ASSESSMENT

ELIMINATION eHF 2 - 4 weeks (*)

IMPROVEMENT NO IMPROVEMENT
(#) preferable to do spec IgE CMP (RAST)
> class 1 : no challenge (without iv line)
< class 1 : challenge without iv line acceptable
and/or skin prick test
SPT pos : no challenge (without iv line)
SPT neg : challenge without iv line acceptable
OPEN CHALLENGE (#)
cows milk formula
Clinical observation
SUSPICION OF COWS MILK PROTEIN ALLERGY

CLINICAL ASSESSMENT

Suspicion of
severe CMPA
Suspicion of
mild/moderate CMPA

ELIMINATION eHF 2 - 4 weeks (*)

IMPROVEMENT
NO IMPROVEMENT
OPEN CHALLENGE (#)
cows milk formula
Clinical observation
SUSPICION OF COWS MILK PROTEIN ALLERGY

CLINICAL ASSESSMENT

Suspicion of
severe CMPA
Suspicion of
mild/moderate CMPA

NO CMPA SYMPTOMS
resume CMP in diet
and monitor
CMPA SYMPTOMS
Maintain CMP
elimination diet
until age 9 - 12 months
for at least 6 months
REPEAT
CHALLENGE
ELIMINATION eHF 2 - 4 weeks (*)

IMPROVEMENT

NO IMPROVEMENT
SUSPICION OF COWS MILK PROTEIN ALLERGY

CLINICAL ASSESSMENT

Suspicion of
severe CMPA
Suspicion of
mild/moderate CMPA

Consider
elimination diet with AAF
or
other diagnosis
and resume CMP in diet
Suspicion of
mild/moderate CMPA
Suspicion of
severe CMPA
Testing for CMPA

SUSPICION OF COWS MILK PROTEIN ALLERGY

CLINICAL ASSESSMENT

REFERRAL TO
PEDIATRIC
SPECIALIST
and
ELIMINATION DIET
Amino Acid Formula (AAF)
minimal for 2 - 4 weeks
NO IMPROVEMENT IMPROVEMENT
Pediatric specialist
Diagnostic procedures
Pediatric specialist
challenge