AIMS AND OBJECTIVES
1- Classification of adverse milk reaction
2- Consider the prevalence of Cow’s Milk Protein Allergy (CMPA) and challenges of diagnosis
3- Review the differences between IgE and non-IgE CMPA
4- Consider What advice should be given to those with IgE mediated CMPA
And how to manage non-IgE CMPA, Considering types of formula and milk Ladder
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Diagnosis and Management of Cow’s Milk Protein Allergy
1. Diagnosis and Management
of Cow’s Milk Protein Allergy
Dr Ola Alkhars
General Pediatric Consultant
27/10/2021
2. AIMS AND OBJECTIVES
1- Classification of adverse milk reaction
2- Consider the prevalence of Cow’s Milk Protein Allergy (CMPA) and challenges of diagnosis
3- Review the differences between IgE and non-IgE CMPA
4- ConsiderWhat advice should be given to those with IgE mediated CMPA
And how to manage non-IgE CMPA, Considering types of formula and milk Ladder
3. Classification of adverse milk reaction
• Lactose intolerance
Sugar
( Lactose)
• CMPA
Protein (whey,
casein)
• Nothing
Fat
4. MAJOR PROTEINS IN COW MILK
Casein (~80% total)
Complexes, give ‘milky ‘
appearance.
10% of all allergy.
Precipitated from skim milk by
acid at pH 4.6.
4 basic caseins( αs1, αs2,β,κ
comprising 32%,28%,10%)
Heat resistant and more allergenic.
Whey (~ 20%)
Β- Lactoglobulin
α-Lactalbumin
Bovin immunoglobulins
Bovin serum albumin
Extensive heating destroys ( bovine serum
albumin, bovine Y-globulin, and α-
Lactalbumin).
5. CASE HISTORY
Liath is a 3 month old who is formula fed
Has no eczema
Has small regurgitate after feeds
Has generally normal stool
He is frequently unsettled and crying in the evening, this lasts a few hours
and then resolves.
6. QUESTION
What is the most likely cause of his symptoms ?
1. Non-IgE Cow’s Milk Protein Allergy
2. Infantile Colic
3. Reflux
7. QUESTION
What is the most likely cause of his symptoms ?
1. Non-IgE Cow’s Milk Protein Allergy
2. Infantile Colic
3. Reflux
8. CASE HISTORY
Nawaf 6 months old boy brought by his parents who are concerned about
allergy
Nawaf was given yogurt for the first time and within 10 minutes developed
urticarial across his face and mild swelling of his eyes. No treatment was
given and his symptoms resolved within an hour, he was otherwise well that
day
Nawaf is Exclusively breastfed and only had bottle of formula at birth
So far, Nawaf has been given some fruits and vegetables with no concerns
Nawaf has no PMH of note.
9. QUESTION
What is the most likely cause ?
1- IgE mediated Cow’s Milk Protein allergy
2-Non- IgE Mediated CMPA
3-Viral illness
10. QUESTION
What is the most likely cause ?
1- IgE mediated Cow’s Milk Protein allergy
2-Non- IgE Mediated CMPA
3-Viral illness
11. CASE HISTORY
Sarah is 3 months old baby who was born at term but needed IV antibiotics
due to aspiration of meconium. Breast fed baby.
Within 2 months of life, Sarah developed widespread eczema. Her parents
report that she is constantly unsettled and crying and they have had
multiple ER and PHC attendances.
She frequently vomits after feeds and has frequent, explosive diarrhea.
12. QUESTION
What is the most likely cause of her symptoms ?
1. Non-IgE Cow’s Milk Protein Allergy
2. Colic
3. Reflux
13. QUESTION
What is the most likely cause of her symptoms ?
1. Non-IgE Cow’s Milk Protein Allergy
2. Colic
3. Reflux
14. QUESTION
If mother wants to continue breast feeding, what should you advise?
1. Start a hypoallergenic formula
2. To continue to breastfeed and exclude all milk products from her diet
3. To continue to breastfeed and exclude all soya products from her diet
4. Continue to breastfeed and exclude all milk and soya products from her
diet.
15. QUESTION
If mother wants to continue breast feeding, what should you advise?
1. Start a hypoallergenic formula
2. To continue to breastfeed and exclude all milk products from her diet
3. To continue to breastfeed and exclude all soya products from her diet
4. Continue to breastfeed and exclude all milk and soya products from her
diet.
16. QUESTION
Mother decided she want to stop breast feeding as she returning to work. what
formula would you recommend ?
1. Any formula she want to buy
2. A soya formula
3. An extensively hydrolyzed formula
4. An amino acid formula
17. QUESTION
Mother decided she want to stop breast feeding as she returning to work. what
formula would you recommend ?
1. Any formula she want to buy
2. A soya formula
3. An extensively hydrolyzed formula
4. An amino acid formula
18.
19. Cow’s Milk Protein Allergy CMPA
(CMPA) is common and Usually they present within the first 3-6 months of
life and rarely after 12 months of age
There can be multiple presentations to PHC/Emergency before diagnosis is
made, especially with non –IgE allergies
Prevalence likely remains unchanged
Rare in Adult 0.49-0.6%
20. EARLY DIAGNOSIS IS IMPORTANT
Cows milk allergy onset usually presents early in life
Diagnosis can be often be delayed which can:
✔Complicate dietary management & lead to feeding difficulties &
✔Increase the risk of developing functional GI disorders in later childhood
Symptoms of cow’s milk protein allergy are also symptoms of other
conditions….. Check the diagnosis!
21. LACTOSE INTOLERANCE
Lactose-carbohydrate- present in Milk/ dairy
products
Enzyme lactase is present on the intestinal
brush border
Lactase’s function is to break down lactose
into the two simple sugars it is made up of,
glucose and galactose.
NO lactase= absorption of water into gut,
colonic fermentation of bacteria
22. SYMPTOMS OF LACTOSE INTOLERANCE
Abdominal pain
Abdominal Swelling
/bloating
Flatulence
Explosive Diarrhea
Onset of symptoms
within 30 min- 2h
24. FGID: FUNCTIONAL GASTROINTESTINAL
DISORDERS
Group of chronic and recurrent
symptoms
Sometimes feeding issues
Functional problem with digestive
system
Without structural or biochemical
abnormalities
Managed solely in primary care
Practical & dietary strategies
Diagnosed against the symptom
based Rome diagnostic criteria
Medical history & physical examination
34. Diagnosis
To date, no shared tolerance markers for the diagnosis of
food allergy have been identified, and OFC remains the
gold standard.
Giannetti, A.; Toschi Vespasiani, G.; Ricci, G.; Miniaci, A.; di Palmo, E.; Pession, A. Cow’s Milk Protein Allergy as a Model of Food Allergies. Nutrients 2021, 13, 1525.
https://doi.org/10.3390/nu13051525
35. CASE HISTORY
Ali is a 4 months old male infant
Was on breastfed briefly for 2 weeks, now on AR formula
Always been a difficult feeder
⮚Cries & arches back when fed
⮚Regurgitates into mouth
⮚Breathless after feeds
On anti –reflux treatment –still symptomatic,
Rx:
⮚Changed to Extensive hydrolyzed formula – all settled,
⮚Challenge test – positive
37. INVESTIGATIONS FOR IgE FOOD ALLERGY
Specific IgE test
Need to be done in conjunction with the history
Given as a number but can also be graded I-IV,
>-0.35 is positive
Positive test do not equal allergy, can be caused
by sensitization
Positive test do not give any indication about the
likelihood of allergy or the severity of reactions
Total IgE has little relevance in food allergy
Components-expensive and best saved for
secondary care
38. SKIN PRICK TESTING
Takes about 15 minutes to perform and get results
Need to stop anti-histamines four days before
Standard panel of allergens that can be tested
Can do prick-prick testing
Often not accessible by most hospitals
40. 100% PPV FOR SKIN PRICK TESTING
(IGE)=> 3MM IS POSITIVE
Cow milk
≥6 mm wheal
Egg
≥ 5mm wheal ( 0-2 yrs age)
≥7 mm wheal
Peanut
≥4mm wheal ( 0-2 yrs age)
≥ 8 mm wheal
SPT > 8 associated with > 95%
likelihood of clinical reactivity
41. ALLERGY PATCH TESTING ( APT)
Relatively recent in the diagnosis of food allergy
Reproducible ( 90% on back )
Safe: 1% risk systemic reaction
Measure T-cell- mediated (Non IgE) responses to food allergens.
Occlusion for 48 hours and read at 72 hours.
Most studies with foods have been performed with cow’s milk, hen’s egg
and wheat only.
APT has a high diagnostic efficacy, than SPT for late phase clinical reactions
( specially if eczema present)
High negative predictive value
42. DIAGNOSTIC TOOLS-IGE MILK ALLERGY
DBPCFC ( double –blind Placebo-Controlled Food Challenge) with medical history is the
most specific and sensitive diagnostic tool.
Risk of serious anaphylaxis, time consuming and expensive!
Detection of specific IgE- for cow’s milk extract or major milk components ( α,β Lacto-
albumin, casein)
Skin prick method ( higher sensitivity)
Serum ( higher specificity)
>95% confidence that no IgE allergy exist. ( High NPV)
Intradermal test (ID) is contraindicated and not predictive!
BAT(Basophil activation test)- serum
Activation of basophils via the IgE- receptor. Increase in surface markers ( CD63 and CD 203c),
which level of expression is measured by flow cytometry
44. WHAT WILL THE ALLERGY TEAM DO?
IgE mediated CMPA or severe non-IgE Mediated allergies –refer to Allergist
Allergy focused history
Targeted investigations- often including skin prick tests to baked milk, milk
solution
Review yearly. Consider if baked milk can be introduced- usually under
guidance of the hospital
48. CHOSING A SPECIALISIT EHF
• Hydrolyzed whey protein is more palatable than casein
based formula. Lactose can improve palatability
Palatability/taste
• Soya not recommended under 6 months of age
Protein 30-35 g
• Not al EHF’s are suitable for a Halal or vegetarian diet
Cultural/religious
49. INDICATIONS FOR AMINO ACID BASED
FORMULA
1. Faltering growth
2. Severe eczema
3. Anaphylaxis
4. Infants still reacting to extensively hydrolysed formula /partially recovery
5. Severe gastrointestinal symptoms (FPIES,EOE)
6. Multiple food allergies
Only about 10% children will need an AAF; however, it is widely over
prescribed
50.
51.
52. ADVICE FOR BREASTFEEDING MOTHERS
Exclusion of diary and potentially soya from diet
Up to 50% react to soya as well as cow’s milk protein (10-14% with an IgE-
mediated cow’s milk protein allergy)
No need to have strict soya avoidance-but avoid using soya as milk substitute
54. CHANGE OF FORMULA
Prescribe 2 tins initially to check compliance/tolerance and then to give
monthly prescription
Smell/taste is much less palatable. Unless there is anaphylaxis, consider
mixing old formula and gradually increasing amount if not initially tolerated
Stool can become green with these formulas
55. FURTHER MANAGEMENT OF NON-IGE
MEDIATED CMPA
After six months exclusion of CMP and usually by 12 months age-cow’s milk
protein can begin to be reintroduced
This is done via the milk ladder
Progressing through the steps does not induce tolerance
However, it will help parents find a stage at which their child may be able
to tolerate some forms of CMP, until their gut matures and they can progress
further
56.
57. PROGNOSIS OF MILK ALLERGY
60-75% outgrow CMPA by aged 2 yrs
Up to 85-90% aged 3 yrs
Review prescriptions
when the patient is over 2 yrs
If formula has been prescribed for over a year
If the child is able to drink cow’s milk or eat yougerts/cheese
If larger quantities are prescribed than suggested according to age/Wt
59. MAJOR DIFFERENCES IN CMPA TYPES &
MANAGEMENT
IgE Mediated Non-IgE mediated
Prevalence ( 2-7%) 55% 45%
Symptom onset Minutes-hours Days-weeks
Severity Life threatening Limited
Persistence Up to teen years! Resolved by 12 months age
Associated disease Asthma,
Rhinitis,Eczema…etc
GERD,Eczema,EOE,..etc
Anaphylaxis risk Yes No
Nutritional support Calcium + others ( multiple!) Calcium
Doctor in charge Allegist GP/Pediatiatian/GI
Testing Serum IgE-SPT No (patch?)
Formula indicated AAF eHF/AAF
Other food allergies? High Risk Low risk
60. References
Baghlaf M. A, Eid N. M. S. Prevalence, Risk Factors, Clinical Manifestation, Diagnosis
Aspects and Nutrition Therapy in Relation to both IgE and IgG Cow’s Milk Protein Allergies
among a Population of Saudi Arabia: A Literature Review. Curr Res Nutr Food Sci 2021;
9(2). doi : http://dx.doi.org/10.12944/CRNFSJ.9.2.02
Abrams EM, Hildebrand KJ, Chan ES. Non-IgE-mediated food allergy: Evaluation and
management. Paediatr Child Health. 2021 Apr 27;26(3):173-181. doi:
10.1093/pch/pxaa131. PMID: 33936337; PMCID: PMC8077207.
NICE Clinical Guideline 116 Food Allergy in Children and Young People. 2011
www.nice.org.uk
Luyt et al. British Society for Allergy and Clinical Immunology (BSCACI) guideline for the
diagnosis and management of cow’s milk allergy, July 2014 www.bsaci.org
Better recognition, diagnosis and management of non-IgE mediated cow’s milk allergy
in infancy: iMAP—an international interpretation of the MAP (Milk Allergy in Primary Care)
guideline by Venter et al; Clin Transl Allergy. 2017 7:26 Available at:
https://ctajournal.biomedcentral.com/articles/10.1186/s13601-017-0162-y (accessed
October 2017)