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

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

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

23. CMPA & LACTOSE INTOLERANCE
SHOULD NOT BE CONFUSED

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

25. FGID: FUNCTIONAL GASTROINTESTINAL
DISORDERS
Regurgitation
Functional diarrhea and
constipation
Colic
Infant dyschezia

26. FGID: FUNCTIONAL GASTROINTESTINAL
DISORDERS
Up to 54.9 % infant
0-6 months
1 symptom or more
Cow’s Milk protein
Allergy 2-5% infants

27. Clinical manifestations of CMPA

28. SKIN

29. GASTROINTESTINAL
IgE-mediated Non-IgE-mediated

31. RESPIRATORY

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

36. KEY MESSAGE-FOOD ALLERGY
Timing Symptoms Reproducible

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

39. SKIN PRICK TESTING

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

43. COMPONENT TESTING –HELP YOUR
MANAGEMENT PLAN !

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

47. CLASSIFICATION OF INFANT AND
SPECIAL FORMULAS

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

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

53. I MAP GUIDELINE

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

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

58. Summary

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)