G cows milk-allergy MRCPCH

1. Louise Wells Page 1 of 11 July 2014
Cows Milk Allergy
Title of Guideline (must include the word “Guideline” (not
protocol, policy, procedure etc)
Guideline for the assessment and
management cows milk allergy
Contact Name and Job Title (author) Dr Jyoti Balain Paediatric Registrar
Dr Louise Wells Consultant Paediatrician
Dr Lisa Waddell Paediatric Dietitian
Ruth Prigg Paediatric Dietitian
Directorate & Speciality Family Health
General Paediatrics
Date of submission 01/08/2014
Date on which guideline must be reviewed (this should be
one to three years)
01/08/2018
Explicit definition of patient group to which it applies (e.g.
inclusion and exclusion criteria, diagnosis)
Infants and children with cow’s milk allergy (IgE
and non IgE mediated)
Abstract This guideline describes the assessment,
investigation and management cow’s milk allergy
(IgE and non IgE mediated)
Key Words Cow’s milk allergy; children; paediatrics
Statement of the evidence base of the guideline – has the
guideline been peer reviewed by colleagues?
Evidence base: (1-5)
1a meta analysis of randomised controlled trials
1b at least one randomised controlled trial
2a at least one well-designed controlled study without
randomisation
2b at least one other type of well-designed quasi-
experimental study
3 well –designed non-experimental descriptive studies
(i.e. comparative / correlation and case studies)
4 expert committee reports or opinions and / or clinical
experiences of respected authorities
5 recommended best practise based on the clinical
experience of the guideline developer
The evidence base is drawn from the research
evidence included in the recent NICE guidance.
The majority of the research pertaining to cow’s
milk allergy is level 3 evidence.
Consultation Process Departmental Clinical Guidelines Meeting
Target audience Medical and nursing staff caring for infants and
children with cow’s milk allergy
This guideline has been registered with the trust. However, clinical guidelines are guidelines
only. The interpretation and application of clinical guidelines will remain the responsibility of the
individual clinician. If in doubt contact a senior colleague or expert. Caution is advised when
using guidelines after the review date.

2. Louise Wells Page 2 of 11 July 2014
The Scope of the Guideline
The purpose of this guideline is to highlight the broad spectrum of manifestations of
cow’s milk allergy and offer the management approach to the diagnosis and
treatment.
Introduction
 Cow’s milk allergy (CMA) is defined as a reproducible adverse reaction of an
immunological nature induced by cow’s milk protein.
 The underlying immunological mechanism distinguishes cow’s milk allergy from
other adverse reactions to cow’s milk such as lactose intolerance and inter‐
current gastrointestinal illnesses.
Prevalence
 The prevalence of cow’s milk allergy is between 1.8% and 7.5% of infants during
the first year of life.
 Cow’s milk allergy commonly presents in infancy with most affected children
presenting with symptoms by 6 months of age.
 Onset is rare after 12 months
Classification
 Cow’s milk allergy can be classified by the underlying immune mechanism into
IgE mediated early‐onset and non‐IgE mediated delayed‐onset types.
 Most infants present within a week of cow’s milk introduction although
presentation may be delayed for many weeks.
 In the majority of children the triggering food is cow’s milk, infant formulas or
cow’s milk based foods (e.g. porridge), although a small number react to cow’s
milk protein in maternal breast milk whilst exclusively breast‐fed.
Table 1 Presentation of IgE and non IgE mediated CMA.
Table 1
IgE Mediated CMA Non Ig E Mediated CMA
Onset of
Symptoms
Within minutes of exposure.
Frequently delayed, several hours and
in some instances several days after
ingestion
Anaphylaxis
risk
Present Not at risk of anaphylaxis
Cutaneous
Symptoms
 Pruritus without skin
lesions
 Urticaria
 Atopic eczema
 Erythema

3. Louise Wells Page 3 of 11 July 2014
 Angio‐oedema
 Atopic eczema
 Erythema
Gastrointestinal
Symptoms
 Vomiting
 Diarrhoea
 Abdominal pain
 Vomiting/Posseting, Poor
response to standard anti‐reflux
medications
 Irritability (Colic), More severe
and frequent
 Dysphagia: Food refusal and
aversion to lumps
 Diarrhoea, Severity varies and
may be associated with faltering
growth and enteropathy with
hypoalbuminemia
 Constipation, distress with
defecation and excessive
straining despite soft stools may
be a feature
 Food protein Induced
Enterocolitis Syndrome (FPIES)
Rare
 Well infant with blood in stools
Caused by allergic distal colitis.
 Usually well, happy, thriving,
breast fed infants present with
blood and mucus streaking in
stools
 Mucus in stools
 Offensive stools
 Excessive flatulence
 Nappy rash/ perianal redness

4. Louise Wells Page 4 of 11 July 2014
 Pallor & tiredness
 Rapid gut transit (milk goes
straight through them)
 Iron deficiency
CNS Symptoms
Irritability
Associated with irritability, back arching
Respiratory
Symptoms
Upper respiratory
Rhinitis:
Nasal congestion/
rhinorrhoea
Sneezing
Lower respiratory
Wheeze
Cough
Stridor
Difficulty breathing
Lethargy
Non‐specific congestion/chestiness
Cardiovascular
Symptoms
Pale, clammy
Anaphylaxis
Clinical Assessment and Diagnosis
 Early and reliable diagnosis is important to initiate the appropriate diet where
confirmed and to avoid unnecessary dietary restrictions if not.
o Diagnosis of IgE mediated cow’s milk allergy
Diagnosis is based on the combination of clinical history and examination.
Skin Prick Tests (SPT) or specific IgE should be used to confirm the diagnosis
in IgE mediated allergy.
Anaphylaxis to milk is potentially fatal. Anaphylaxis may manifest in infants
as pallor and floppiness. Clinicians should therefore elicit a complete
history of all symptoms carefully to assess the severity of reaction.
Intramuscular adrenaline (epipen) should be prescribed for emergency use
if there is history suggestive of anaphylaxis

5. Louise Wells Page 5 of 11 July 2014
Algorithm of diagnosis of IgE Mediated CMA with Skin Prick Tests (SPTs)
and Cows Milk Protein Specific IgE (CMP SpIgE)
Table 2
Positive Predictive values (PPV) for food specific IgE and SPTs to cow’s milk
>95% specific Ig E PPV Age < 2 years 5 kU/L
Age > 2 years 15 kU/L
>95% SPT PPV
All children 7 mm
Age < 2 years 5 mm
Typical History of IgE
Mediated CMA (Table 1)
SPT
SPT weal
diameter
IgE‐
mediated
Milk allergy
likely
Repeat SPT and/ or consider
serum specific IgE
IgE
mediated
CMA
excluded
Consider oral cow’s milk
challenge
SPT
Atypical history
SPT weal
diameter > 3mm
<3mm
> 5mm
If repeat SPT neg
and/or SpIgE CMP
grade 0
>Grade 1 IgE
CMP
2‐ 4mm
0‐1mm
> 3mm

6. Louise Wells Page 6 of 11 July 2014
o Diagnosis of non IgE mediated cow’s milk allergy
Diagnosis is entirely based on clinical history and examination and
currently there are no suitable diagnostic tests available. Diagnosis is
made by resolution of symptoms on cow’s milk exclusion, followed by
recurrence of symptoms on re‐introduction. If moderate / severe eczema
is the main presenting symptom then please refer to the ‘food allergy in
eczema’ guideline.
Elimination diet for 4‐6 weeks and review
using appropriate milk as below
Clinical suspicion of non IgE mediated CMA (See Table 1)
Diagnose with Non IgE
mediated CMA
Consider other
diagnoses
Clear and dramatic
improvement of
symptoms
No change in symptoms
Re‐introduce cow’s milk
Recurrence of
symptoms
No significant difference
Retry elimination using an AA
formula
No change in symptomsClear and dramatic
improvement of
symptoms

7. Louise Wells Page 7 of 11 July 2014
Management of both IgE and non IgE mediated CMA
Management Principles
1. Dietary avoidance
2. Choice of milk substitute
3. Calcium availability and replacement
4. Energy and protein adequacy
5. Reintroduction
6. Oral tolerance
Dietary Avoidance
 The mainstay of treatment is complete avoidance of cow’s milk and foods
containing cow’s milk.
 Verbal and written advice should be provided on the avoidance of dairy based
solids and foods with cow’s milk proteins as hidden ingredients and measures to
avoid contamination. (see parent information sheet)
 Advice should be adapted to the age of the child and include education to other
carers e.g. grandparents, child‐minder, nurseries to minimise accidental
ingestion.
 All children with confirmed diagnosis of cow’s milk allergy should be referred to a
paediatric dietitian.
 Children should be reviewed at least 6 monthly intervals for assessment of
nutritional adequacy, revision of appropriate milk substitute, tolerance and
possible cow’s milk reintroduction.

8. Louise Wells Page 8 of 11 July 2014
Choice of milk substitute
i) Breast fed Infants
ii) Non Breast fed Infants
Hypoallergenic Formulas (contact the dietitian for details of specific milks)
Continue breast feeding
Infant > 6 months should be given vit D supplementation
(ABIDEC 0.6mls od)
Dietary exclusion of cow’s milk in lactating mother
Calcium and vitamin supplementation of mother
AA formula to supplement breast milk if required
Consider other diagnoses
Consider multiple food allergy e.g. soya/ wheat
Trial of AA formula in place of breast milk or trial
multiple exclusion diet for breast feeding mum (refer to
a dietitian)
Symptoms persist
Symptoms persist
Diagnosis of CMA
Amino acid formula (AA)
Extensively hydrolysed formula (EHF)
Does the infant have:
Multiple food allergies
Severe systemic reactions to trace amounts e.g. anaphylaxis
Severe infantile atopic eczema
Inability to tolerate milk from a breastfeeding mum on a normal diet
Eosinophilic oesophagitis
Severe enteropathy/ colitis
Faltering growth
Symptoms persist
Yes
No

9. Louise Wells Page 9 of 11 July 2014
Calcium availability and replacement
 Cow’s milk and dairy products are the principle sources of dietary
calcium.
 A dietitian should assess all children on cow’s milk exclusion diets for
adequacy of calcium intake
Reintroduction
 Cow’s milk allergy mostly resolves during early childhood. The speed with
which this tolerance develops varies greatly. Therefore, timing and
appropriateness of reintroduction should be individually assessed.
 Non IgE mediated allergy is more likely to resolve earlier than IgE
mediated allergy.
Reintroduction in non IgE mediated CMA
Reintroduction should be attempted any time after 6 months of age. Open
challenge at home is appropriate for almost all patients via a milk ladder
available from the dietician.
Cow’s milk is gradually introduced in the diet, usually starting with baked
foods. If symptoms re‐appear, the exclusion diet is continued for another 6
months and reintroduction attempted again.
Soya formula should not be used in infants less than 6 months
If over 6 months of age and soya infant formula is considered because of lower cost and
palatability, tolerance to soya protein should first be established by gradual introduction.
Caution should be taken in recommending it to infants with gut symptoms due to the risk of
cross‐reactivity between cow’s milk and soya.
Exceptions may arise where for example; refusal to take EHF/AA places the infant at nutritional
risk or in vegan families unable to breast feed or symptomatic with breast milk
AA formulas are suitable first line formulas for CMA but are usually reserved because of higher cost
for those infants who do not tolerate EHF.
AA follow on formulas are available for use in children over 1 year old. They are indicated when
milk allergic infants (who meet the criteria for an AA milk) require additional energy, calcium and
iron or a flavoured product.

10. Louise Wells Page 10 of 11 July 2014
Reintroduction in IgE mediated CMA
,
Desensitisation (Oral tolerance)
Oral tolerance induction is indicated in children where CM allergy persists
beyond an age at which it is expected to resolve.
It involves administration of increasing doses of cow’s milk during an
induction phase, starting with a dose small enough not to cause a reaction
and continuing to a target dose or until the treated individual’s symptoms
preclude further dose increments. This is followed by a maintenance phase
with regular intake of the maximum amount of cow’s milk.
Indications for oral tolerance needs to be discussed with the Consultant and
needs referral to the regional paediatric allergy centre at Leicester Royal
Infirmary (0300 303 1573).
History of severe reaction with accidental
exposure in last 6 months
Yes
No
Defer consideration of
reintroduction for 6
months
Consider reintroduction at 1 year of age
History of severe reaction/anaphylaxis to CMA
Severe uncontrolled asthma
Atopic background
Parents unable to comprehend or adhere to protocol
Clinician’s discretion
Yes to any of above
Above risk factors absent
Home reintroduction using
milk ladder (available from
the child’s dietitian)
Challenge in Hospital
SPT or Specific IgE low or negative or
significant reduction from diagnosis
Yes
No

11. Louise Wells Page 11 of 11 July 2014
Follow up.
o All children with CMA should be followed up by their GP or a paediatrician as
up to 95% outgrow their allergy by the age of 5. They should be reviewed
regularly to determine whether reintroduction is appropriate as per the
guidelines.
o Non IgE mediated CMA can be managed within the primary care
setting by the GP and community dietician.
o IgE mediated CMA can be managed in the primary care setting as per
the reintroduction in IgE mediated CMA algorithm for home
introduction BUT NOT if they require hospital challenge.
Abbreviations
CMP Cow’s milk protein
EHF Extensively Hydrolysed Formula
AA Amino acid formula
SPT Skin Prick Test