Zakiudin Munasir

COW’S MILK PROTEIN

ALLERGY MANAGEMENT

Nutritional Intervention
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Prof. DR. Dr. Zakiudin MUNASIR, SpA(K)

Division of Allergy and Clinical Immunology, University of Indonesia,
Jakarta, Indonesia
Professor Doctor Zakiudin Munasir is Head of the Division of Allergy and Immunology, Department of Child Health in the
Faculty of Medicine, University of Indonesia - Cipto Mangunkusumo Hospital.

He completed his medical degree at the University of Indonesia, Jakarta, Indonesia and residency in paediatrics.

Professor Munasir subsequently became a pediatric consultant in allergy and immunology for the Indonesian Pediatric
Society.

Professor Munasir is a member of the working group on allergy and immunology for the Indonesian Pediatric Society and also
a member of the Indonesian Allergy and Immunology Association.

He is a member of the European Pediatric Allergy Rheumatology, the World Allergy Organization, the European Academy of
Allergy and Clinical Immunology and board member of Asia Pacific Association of Pediatric Allergy, Respirology & Immunology
(APAPARI).
He is also an editor for the Asia Pacific Allergy Journal.

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Allergy-Prevalence

Cow’s milk protein is the second most Indonesia national data is lacking.
common food allergen in young Asian
children, after egg.

Lee AJ, Thalayasingam M, Lee BW, Asia Pac Allergy 2013;3:3-14

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Sensitization on atopic dermatitis patients

in Pediatric Allergy Clinic (2011, 2013)

2. Sidabutar S, et al. Sari Pediatri. 2011;13:147-51.

3. Munasir ZM, Muktiarti D. Asia Pac Allergy. 2013; 3: 23–8.

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The proteins in cow’s milk

Fraction/protein Allergen [1] g/l ~30 % Total protein 80 MW (kDa) AA PI
Caseins
Alphas1-casein 12-15 29 23.6 199 4.9-5.0
Alphas2-casein 3-4 8 25.2 207 5.2-5.4
Beta-casein 9-11 27 24.0 209 5.1-5.4
Gamma1-casein Bos d 8 20.6 180 5.5
Gamma2-casein 1-2 6 11.8 104 6.4
Gamma3-casein 11.6 102 5.8
Kappa-casein 3-4 10 19.0 169 5.4-5.6
~5.0 20
Whey proteins
Alpha-lactalbumin Bos d 4 1-1.5 5 14.2 123 4.8
Beta-lactoglobulin Bos d 5 3-4 10 18.3 162 5.3
Immunoglobulin Bos d 7 0.6-1.0 3 160.0 - -
BSA Bos d 6 0.1-0.4 1 67.0 583 4.9-5.1
Lactoferrin - 0.09 traces 800.0 703 8.7
AA = Amino acids; BSA = bovine serum albumin.
Alessandro F, et al. Cow’s Milk Allergy in Children and Adults.

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CMPA-suspected symptoms

Gastro-
Atopic esophageal Other GI
Dermatitis Infantile colic symptoms
reflux

Milk diarrhea Vomiting,

and rectal chronic diarrhea,
bleeding failure to thrive

Apps JR and Beattie RM, BMJ 2009:339:b2275

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The spectrum of conditions

associated with IgE-mediated
reactions to cow’s milk
I Systemic IgE-mediated reactions (anaphylaxis)
A Immediate-onset reactions
B Late-onset reactions

II IgE-mediated gastrointestinal reactions

A Oral allergy syndrome
B Immediate gastrointestinal allergy

III IgE-mediated respiratory reactions

A Asthma and rhinitis secondary to ingestion of milk
B Asthma and rhinitis secondary to inhalation of milk (e.g. occupational asthma)

IV IgE-mediated cutaneous reactions

A Immediate-onset reactions
1. Acute urticarial or angioedema
2. Contact urticarial
B Late-onset reactions
Atopic dermatitis

Boyce JA, Assa’ad A, Burks AW, et al: Guidelines for the diagnosis and management of food allergy in the United States: report of the NIAID-sponsored expert panel. J. Allergy Clin Immunol 2010;126(6 suppl):S1-S58.

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The Management of Cow’s Milk Allergy

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Diet
• Free of cow’s milk protein.

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BREAST FEEDING IS
THE BEST
Compounds IMMUNOMODULATOR
with immunological properties in human milk

Anti-microbial compounds Immune development

Immunoglobiuines: sIgA, SIgG, compounds
SIgM Macrophages
Lactoferrin, lactoferrin B and H Neutrophils
Lysozyme Lymphocytes
Lactoperoxidase Cytokines
Nucleotide-hydrolizing Growth factors
Antibodies Hormones
к-casein and α-lactalbumin Milk peptides
Haptocorrin Long-chain polyunsaturated
Mucins fatty acids
Lactadherin Nucleotides
Free secretory component Adhesion molecules
Oligosaccharides and pre-
biotics Anti-inflammatory compounds
Fatty acids Cytokines: Il-10 and TGFβ
Maternal leukocytes and Il-1 receptor anatagonist
Cytokines TNFα and Il-6 receptors
sCD14 sCD14
Complement and complement Adhesion molecules
receptors Long-chain polyunsaturated
β-defensin-1 fatty acids
Toll-like receptors Hormones and growth factors
Bifidus factor Osteoprotegerin
Tolerance/priming compounds Long-chain polyunsaturated
Cytokines: Il10 and TGFβ fatty acids
Anti-idiotypic antibodies Hormones and growth factors

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Feeding and Formula Options

for Infants with CMA
Breast milk with
maternal diet restriction

Extensively hydrolyzed • Contains only peptides that have a MW <3,000 d

formula (eHF) • Soy-based formula

Free amino acid-based • peptide-free formulas that contain mixtures of

formula (AAF) essential and nonessential amino acids

Formulas that should • Partially hydrolyzed formula (pHF) - Contains reduced

NOT be used oligopeptides that have a MW generally <5,000 d
Greer FR, et al. Pediatrics 2008;121:183-91

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Should Allergenic Foods Be

Restricted During Lactation?

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Sensitization

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Extensive
Hydrolysate
CM Protein
Formula

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• Extensively hydrolyzed and free amino

acid-based formulas have been
subjected to such studies and are
hypoallergenic
• Pediatrics August 2000, 106 (2) 346-349; DOI: https://doi.org/10.1542/peds.106.2.346

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 What is Hydrolyzed Formula
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(HFs)
• Formulas contain cow milk proteins (CMPs) that are subjected to chemical and enzymatic
hydrolysis to reduce the molecular weight, the peptide size, and, consequently, the allergenicity
of the proteins.
Cow’s milk based formulas with intact 14 kD (α-lactabumin) to 67 kD (bovine serum
proteins albumin)

pHFs Oligopeptide → molecular weight generally <5 kD

(ranges between 3 and 10 kD)
18% peptide > 6 kD
eHFs >90% a molecular weight of < 3 kD
1 – 5% peptide > 3,5 kD
To be acts as an allergen Peptides to be in range 10-70 kD (mainly 10-40kD)

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eHF and Soy Formula

Both ESPGHAN and AAP recommend eHF based on cow’s milk protein – or
amino acid-based formulas if eHF is not tolerated – as being preferable to
soy protein–based formulae for infants with cow’s milk protein allergy.

However they state that a soy formula may be considered under certain
circumstances in an infant with cow’s milk protein allergy who is older than 6
months.

These circumstances are: if eHF is not accepted or tolerated by the child; if

these formulae are too expensive for the parents; or if there is a strong
parental preference (eg, a vegan diet).
Pediatric Gastroenterology and Nutrition. 2012;55(2):221-229

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Selection of Formula
Three types of infant formula (soy, extensively hydrolysed and amino acid) may be
appropriate for treating cows milk protein allergy.

Selection of a formula depends on the allergy syndrome to be treated.

Extensively hydrolysed formula is recommended as first choice for infants under 6 months
of age for treating immediate cows milk allergy (non-anaphylactic), food protein-induced
enterocolitis syndrome, atopic eczema, gastrointestinal symptoms and food protein-induced
proctocolitis.

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Free lactose and MCT formula

• Free lactose formula is not for CMA
• The majority of infants with CMA can tolerate lactose, except
when an enteropathy with secondary lactase deficiency is
present1
• MCT formula is not for CMA. MCT formula is Suitable for
treatment of food/CM allergy with malabsorptive
enteropathy, as recommended by ESPGHAN2

• 1. World Allergy Organization Journal volume 10, Article number: 41 (2017)

• 2. Arch Dis Child 1999;81:80-4.
•

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J Clin Allerg Immunol 2003; 112:S118-27

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• The allergic march of childhood describes an

association between atopic dermatitis, IgE-
mediated food allergy, allergic asthma, and
allergic rhinitis that begins with an atopic
family history.

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Curr Opin Pediatr. 2014 Aug;26(4):516-20.
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ATOPIC MARCH

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 “ASI adalah yang terbaik”
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 “ASI adalah yang terbaik”
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 “ASI adalah yang terbaik”
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THANK YOU
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THANK YOU

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