Cows milk allergy

CASE 1

• 6 mo male infant , exclusively breast fed.

Mild eczema
Offered baby yogurt as weaning food
Immediate symptoms after one mouthful
-Havies over face and chest
-Forceful vomiting
-Rapidly recovered
-Lab : SPT /sIgE positive
-Rx : milk free diet ,improved
CASE 2

• 4 mo male infant
breast fed briefly for 2 weeks ,now on AR formula
always been a difficult feeder
.cries and arches back when fed
.Regurgitates into mouth
.Breathles after feeds
On anti-reflux treatment and still symptomatic
Rx:
Changed to eHF –improved
Challenge test –Positive
 INTRODUCTION

• Cows’ milk is the commonest food allergen recognized to affect gastrointestinal motility in
children

• Most cases of milk allergy is via non-IgE mediated reactions

• Cows’ milk allergy (CMA) affects 1–7% of children

• CMA peaks in the first year of life and falls to <1% in children 6 years of age and older

• Up to 32–60% of cases report gastrointestinal symptoms

• Up to 5–90% have skin manifestations

• while anaphylaxis affects 0.8–9% of patients .

 INTRODUCTION CONT….

• Persistence of CMA is more likely in children with IgE-mediated CMA or other atopic diseases, multiple food
allergies or with an atopic parent

• Infants with CMA manifested by reflux, irritability or diarrhea may grow up to be school-aged children with
constipation.

• Without an appropriate diagnostic workup ,there is a high risk of both over-and underdiagnoses, and thus
over – and under- treatment.

• There is a confusion between CMPA and lactose intolerance

• Exclusive breast milk infants may also develop clinically significant CMPA via diary proteins transfer into
human breast milk
 NUTRITIONAL VALUES OF MILK

Carbohydrates – Human milk contains mainly lactose ,with small proportion of oligosaccharides
Oligosaccharides are important in the host defense of the infants .

Lipids – represents approximately 50% of the calorie intake.

Fatty acids in human milk consist of a high proportion of long –chain fatty acids (palmitic ,oleic ),
and the essential fatty acids .

Proteins - 70% of human milk proteins are in the soluble whey , 30 insoluble casein.
 whey is easly digested and is associated with more rapid gastric emptying .
 The major human whey protein is alphalactalbumin .

 While the major bovine whey protein is beta-lactoglobulin,and casein which may contribute to
protein allergy and colic
COMPARISON OF BREAST MILK AND COW
MILK PROTEIN
ADVERSE REACTION TO FOOD DIVIDED
TO:
• Food intolerance –Physiologic response like lactose intolerance ,IBS ,
IBD

• Food allergy –Defined as adverse health affection from a specific

immune response that occurs following exposure to antigenic food
component

• The immune reaction my be IgE mediated ,non- IgE mediated ,

mixed
CLASSIFICATION OF ADVERSE REACTION
TO FOOD
DEVELOPMENT OF ALLERGIC INFLAMMATION
 MECHANISM OF MILK ALLERGY

• The major allergens –the Beta-lactoglobulin and casein fraction of proteins (@s1,@s2,B ,and k-casein).

• There is some cross-reactivity with soy protein , particularly in non-IgE mediated allergy.

• Tow mechanisms of allergy –IgE and non IgE mediated

• Tow stages :

• Sensitization

-In genetically predisposed individual –exposure to antigen leads to TH2 type response
-Cytokinase (IL4,IL5,IL10 and IL 13) promotes IgE production
• Activation :

-Inflammatory response –eosinophils , mast cells, neutrophils , and natural killers cells
MECHANISM OF MILK ALLERGY
 RISK FACTORS FOR FOOD ALLERGY (FA)

Genetic ( if both parents are atopic risk for child to have allergic disorder is 50% ,
if one parent is atopic drops to 20%, if neither atopic then risk is 10%)
Environmental factors, affecting barrier function (skin, gut) and immune
pathways.
These include race/ethnicity (non-white children at increased risk), gender,
microbiota, drugs (i.e., antibiotics and acid inhibitors), hygiene, reduced exposure
to siblings, day care and animals, vitamin D insufficiency, comorbidity (i.e., obesity,
dermatitis), multiple dietary factors (such as reduced consumption of omega-3-
polyunsaturated fatty acids, antioxidants or fibre), gastrointestinal infection and
stress
WHY ARE INFANTS AT RISK?

• Digestive enzymes are not fully active

• Immature secretory IgA.
• Increased permeability of mucosa
• Undigested proteins reach immune system
• Reduced gastric acidity and intake of PPI –additional risk
 HIGH RISK FOODS TO ALLERGY

.
 CMA AND GERD

• Persistent regurgitation, vomiting, distress and crying are common symptoms

in the first year of life, often coexist in the same patient and can be related to
CMA.

• The real prevalence and the mechanisms underlying the association between
CMA and GERD are not yet fully clarified

• The association of CMA-GERD was reported in 16–56% of cases with persistent

gastrointestinal symptoms and suspicion of GERD
 CMA AND CONSTIPATION
 Constipation is the most frequent delayed clinical manifestation of CMA

 Some children with CMA switch from diarrhea in infancy to constipation around the time of toilet training

 Shorter duration of breastfeeding and early exposure to CM may play a role in the development of
constipation and anal fissure in infants and young children

 Approximately a fifth of children with CMA-related constipation have multiple food allergy

 Constipation in food allergy has been classified as a non-IgE mediated manifestation, and testing for food-
specific IgE, via skin prick, RAST or immune-CAP testing is uninformative
 IS IT MILK ALLERGY?

Clostrum is the perfect first food for babys .

It may be only a few teaspoons at a time but it Contains nutrients
and provides antibodies to the baby

Foremilk –is what the baby receive at the beginning of breast feeding
Contains a lot of lactose and proteins and very little fat .

Hindmilk – received at the end of breastfeeding ,contains more fat and calories .
 IS IT MILK ALLERGY?
• A forceful letdown and oversupply of milk can also result

in foremilk/hindmilk imbalance and its sequela , mimicking reflux

• Foremilk/ hindmilk imbalance is common in the first 12wks

of lactation .

• Moving to the second breast too readily prior to emptying

the first breast can lead to imbalance and consequent oversupplying

of lactose ,resulting on painful burping ,regurgitation ,colic and explosive stools
 LACTOSE INTOLERANCE
• Lactose intolerance is due to the lack of the enzyme lactase in the small intestines to
break lactose down into glucose and galactose.
• There are four types:
 Primary lactose intolerance occurs as the amount of lactase declines as people grow up.
 Secondary lactose intolerance is due to injury to the small intestine. Such injury could be
the result of infection(Post G\E), celiac disease, inflammatory bowel disease, or other
diseases.
 Developmental lactose intolerance may occur in premature babies and usually improves
over a short period of time.
 Congenital lactose intolerance is an extremely rare genetic disorder ( is most common in
Finland, where it affects an estimated 1 in 60,000 newborns) in which little or no lactase is
made from birth.
 MILK PROTEIN ALLERGY VS LACTOSE
INTOLERANCE
Milk allergy Lactose intolerance
Cause An allergic to the protein in milk and A negative reaction to the
milk products sugar(lactose) in milk and milk
products
Symptoms Persistent diarrhea Bloating
Vomiting Gassiness
Skin rashes Diarrhea
Extreme fussiness
Low or no weight gain
Gassiness
Wheezing
Age at onset First few weeks or months of life Can develop at any age but
Symptoms usually resolves at age of 3- usually not in infants
4 Usually dose not go away
Treatment If the infant is breastfed :mother should Avoid products with lactose
remove all milk protein from here diet (including breast milk )
If the infant is bottle fed –switch to Some amount of lactose may be
hydrolyzed or AA formula tolerated by most of persons
 Diagnosis of CMPA
 THE FIRST STEP IS A THOROUGH HISTORY AND PHYSICAL
EXAMINATION

 In most cases with suspected CMPA,the diagnosis needs

to be confirmed or excluded by an allergen elimination
and challenge procedure

Children with gastrointestinal manifestations of cmpa

are more likely to have negative specific IgE test results
compared with patients with skin manifestations

Specific IgG antibodies or determination of IgG

antibodies or IgG subclass antibodies against CMP has no
role in diagnosing CMPA and not recommended

ESPGHAN GUIDELINES 2013

CoMiSS –Cows milk related symptoms score
Symptom Score
0 ≤1 h/day

1 1–1.5 h/day
2 1.5–2 h/day
Crying * 3 2 to 3 h/day
assessed by parents & without any obvious cause ≥1 week
4 3 to 4 h/day
5 4 to 5 h/day
6 ≥5 h/day
0 0–2 episodes/day
1 ≥3–≤5 x of volume < 5 mL
2 >5 episodes of >5 mL
3 >5 episodes of ±half of the feed in < half of the feeds
Regurgitation *
≥ 1 week continuous regurgitations of small volumes >30 min after each
4
feed
regurgitation of half to complete volume of a feed in at least
5
half of the feeds
6 regurgitation of the complete feed after each feeding
4 hard stools
Stools * 0 formed stools
Brussels Infant and Toddlers Stool Scale (BITSS) 4 loose stools
No change ≥ 1 week
6 watery stools

0 to 6 Atopic eczema ≥1 week

Head neck trunk Arms hands legs feet
Absent 0 0

Skin symptoms Mild 1 1

Moderate 2 2

Severe 3 3
0 or 6 Acute urticaria * and/or angioedema * (no 0/yes 6)
0 no respiratory symptoms
Respiratory symptoms * 1 slight symptoms
≥1 week 2 mild symptoms
3 severe symptoms
Additional information to consider
Worsening of existing eczema might be indicative of CMA
If urticaria/angioedema can be directly related to cow’s milk (e.g., drinking milk in the absence of other food) this is strongly suggestive of CMA.
Brussels infant and toddler stool
scale
 DIAGNOSTIC PROCEDURES

• History and physical examination

• Allergen elimination and challenge procedure .
• Determination of specific IgE and (SPT)-skin prick test (any one)
-IgE – sensitivity 87%, specificity -48%
-SPT- sensitivity 88%, specificity 68%

so negative test does not rule out CMPA

 ENDOSCOPY AND HISTOLOGY

• Unexplained significant and persistent GI symptoms ,

FTT, IDA .
• Neither sensitive nor specific for CMPA.
• Helps for diagnosis other than CMPA.
 CMA MANAGEMENT
 DRACMA, ESPGHAN and AAP guidelines for the nutritional management of CMA-diagnosed
infants.

All guidelines strongly agree that breastmilk is the gold standard for infant
nutrition, including CMA-diagnosed infants, in the first 6 to 12 months of life.

When, BF is not possible, the three guidelines agree that EHF should be the first
treatment option for mild-moderate symptoms

If the infant/child does not tolerate EHF, DRACMA, ESPGHAN, and AAP recommend
the use of AAF.
 CMA MANAGEMENT

 Exclusively, in severe CMA presentations (e.g., anaphylaxis, Heiner syndrome, FPIES,

EoE, and severe enteropathy), AAF should be the first option of treatment (DRACMA and
ESPGHAN)

 Both DRACMA and ESPGHAN recommend that in infants older than 6 months with IgE-
mediated CMA, Soya based formula can be used if there is no cross-reactivity with CMP.

 The three guidelines concur that pHF and other mammalian milks are not recommended
for the nutritional management of CMA, and as such, should be avoided in infants where
CMA has been diagnosed.
 SOYA -PROTEIN FORMULAE

• Soya protein –based formulae are tolerated by the majority of

infants ,but between 10%-20% of affected infants react to soya
protein ,with higher proportions in younger than 6mons .

• The ESPGHAN and the APP recommend that cows –milk –based
formulae should be preferred over soya formula in healthy
infants ,and soya protein based formulae should not usually be
used during the first 6mons of life .
NUTRITIONAL DISADVANTAGE OF
SOYA FORMULA
 Their absorption of minerals and trace elements may be lower because of there
phytate content .
 The contain appreciable amount of phytoestrogen -isoflavones with a weak
estrogenic action that can lead to high serum concentration in infants- which can
mimic estradiol action
 isoflavones are often believed to negatively affect a baby’s sexual, immune, or brain
development.
 However, human studies have found little to no differences in development between
babies fed soy- or cow’s-milk-based formula.
SOYA FORMULA MAY BE CONSIDERED IN AN
INFANTS WITH CMPA

 Older than 6 months if eHF is not accepted or tolerated by the child ,

 If these formulae are too expensive for the parents ,or not available ,
 If there are strong parental preference (eg. vegan diet)
 PROBIOTICS AND CMPA

• Evidences show that probiotics may promote the gut immune regulation
and the allergenic tolerance

Lactobacillus rhamnosus GG for Cow's Milk Allergy in Children: A Systematic

Review and Meta-Analysis

Conclusion: they found that LGG may have moderate-quality evidence

to promote oral tolerance in children with CMA and may facilitate recovery
from intestinal symptoms.

Published online 2021 Oct 22

 PROGNOSIS FOR CMPA

 Most children outgrow IgE- mediated milk allergy by 5-6 years

 Non IgE mediated usually outgrown earlier ,and most of them

before age of 18-24 months
 Approximately 50% of affected children develop tolerance by
the age of one year ,
 >75% by age of 3 years ,and
 >90% are tolerant at age of 6years .
 CAN TOLERANCE TO CMP BE
PREDICTED ?
• Studies showed the resolution of IgE-mediated allergy depend on IgE
level,
patients with persistent CMPA had higher level of IgE in the first 2 years
of life .

• The higher the peak IgE level, the lower the chance of tolerance

• Presence of asthma and allergic rhinitis predicted delayed development

of tolerance
 PREVENTION

 Exclusive breastfeeding is recommended for at least 4months and up to 6 months

of age.

 To possibly reduce the incidence of atopic dermatitis in children younger than 2 years.

 To reduce early onset wheezing before 4 years of age, but not necessarily to reduce asthma .

 To reduce the incidence of CMPA in the first 2 years of life .

 There is no clear effect of breastfeeding on allergic rhinitis .

 TAKE HOME MASSAGES

• CMPA is an immune mediated abnormal reaction to a protein in cow’s milk

• CMPA is thought to occur in 2%-7% of babies world wide and occurs in approximately
0.5% of breastfed infants .

• Risk factors for CMPA include having a parent or sib with allergic disease ,such as
asthma , eczema, and seasonal allergies
 TAKE HOME MASSAGES

• There are no specific diagnostic testes for CMPA .

• The best diagnosis is made by considering a child’s history and examining symptoms

• A monitored food challenge may be used to confirm suspected cases

• Treatment involves eliminating cow’s milk from an infant’s diet and from the diets of
breastfeeding mothers

• Most cases resolves on their own by 6 years of age.