The GP Infant Feeding Network UK: Milk Allergy in Primary Care (MAP) Guideline 2019

WHO guidance

• Babies should be exclusively breastfed until 6 months.

• Complementary solid foods can be introduced from 6 months.

• There is significant evidence for benefits to mother and baby from continued breastfeeding until at least 2 years of age.

NICE and the Scientific Advisory Committee on Nutrition (SACN) guidance

• All pregnant women should take a supplement of 10mcg/day vitamin D during pregnancy and continue to take this when breastfeeding.

• Everyone over one year of age should take a 10mcg/day vitamin D supplement and, as a precaution, breastfed babies from birth up to one year of age should also be given a supplement of 8.5-10mcg/day vitamin D. 

• Babies who are formula fed do not require vitamin D if they are having 500ml/day of infant formula or more, as infant formula already has added vitamin D.

Classification

1. IgE-mediated Cow's milk protein allergy
   Development of serum-specific IgE antibody against cow's milk protein.
   There are immediate and consistently reproducible symptoms which affect multiple organs systems.
   Reactions typically occur usually within 20–30 minutes

2. Non-IgE-mediated Cow's milk protein allergy
   T-cell-mediated mechanism and reactions are typically delayed.
   They usually manifest between 2 and 72 hours after cow's milk ingestion

3. Mixed IgE and non-IgE Cow's milk protein allergic reactions
   Involve a mixture of both IgE and non-IgE responses and are typically delayed

Symptoms of lactose intolerance

Arises from a temporary reduction of gut lactase enzyme.
Symptoms may overlap with those of non-IgE-mediated cow's milk allergy if there is cow's milk-induced enteropathy, and may present with abdominal pain, bloating, and explosive diarrhoea typically 30–60 minutes following ingestion of lactose-containing foods.

Aetiology

Cows’ Milk Allergy (CMA) is an allergy to cows’ milk protein or to the carbohydrate (galactose-alpha-1-3-galactose).

Prevalence

Almost all cases present before one year of age, with a prevalence of between 1.8–7.5% of infants during the first year of life.

The most common presentation is mild-to-moderate non-IgE-mediated allergy.

Risk factors

• Cow’s Milk formula fed or mixed-fed compared to exclusively breastfed infants

• Male sex

• Known food allergy

• Atopic conditions, such as asthma and atopic eczema

Complications

1. Stress and anxiety

2. Restricted diet and malnutrition, including faltering growth because of inadequate nutritional intake through dietary restriction

3. First stage of the so-called 'allergic march': asthma, atopic eczema, and allergic rhinitis.

4. Rarely, severe and life-threatening reactions anaphylaxis following cow's milk ingestion in sensitized children.

5. Cow’s milk enterocolitis, enteropathy, and proctocolitis
   Non-IgE-mediated allergy
   Presents as food protein-induced enterocolitis syndrome (FPIES) involving the entire gastrointestinal tract:
   Symptoms: severe vomiting, diarrhoea, hypotension and collapse after milk ingestion
   Other symptoms: cow's milk-induced enteropathy (which involves the small bowel and may cause secondary lactose intolerance)
   Other symptoms: proctocolitis (which involves the rectum and colon causing mild rectal bleeding and mucus in stools).

6. Eosinophilic oesophagitis
   Non-IgE-mediated allergy
   Presents with combination of vomiting, food aversion, and faltering growth in an infant.

7. Heiner's syndrome
   This is a rare milk-induced pulmonary disease.
   Severe cases may be complicated by pulmonary haemosiderosis, which may present with anaemia or haemoptysis.

Prognosis

Up to 90% of children will grow out of their allergy by age 3.
In general, non-IgE-mediated allergy is associated with a faster rate of resolution than IgE-mediated allergy .

IgE-mediated cow's milk allergy is more likely to persist in children with:

• Personal of family history of atopy (asthma, eczema, allergic rhinitis)

• Severity of symptoms

• Personal history of multiple food allergies

Non-IgE-mediated (delayed onset)

Speed of symptom onset
Typically delayed (usually 2–72 hours after ingestion)

Symptom onset after ingestion after large amount of milk

Skin
Pruritus, erythema, atopic eczema

Gastrointestinal
GORD, colicky abdominal pain, diarrhoea
Constipation
Food refusal or aversion
Perianal redness, blood/mucus in stools

Faltering growth

Lower respiratory tract symptoms
Cough, chest tightness, wheezing

IgE-mediated (immediate onset)

Speed of symptom onset
Typically rapid onset (within minutes and up to 2 hours after ingestion)

Symptom onset after ingestion of small amount of milk

Skin
Pruritus, erythema, atopic eczema
Acute urticaria, acute angio-oedema [lips, face, eyes]

Gastrointestinal
Oral cavity angio-oedema, pruritus
Nausea, vomiting, colicky abdominal pain, diarrhoea

Respiratory tract
Acute rhinitis and/or conjunctivitis
Cough, chest tightness, wheezing

Assessment: aim to distinguish between IgE- and non-IgE-mediated cow’s milk protein allergy

1.Allergy-focused history and examination

Symptoms, in particular, speed of symptom onset AND quantity of milk ingested
GIT Symptoms: gastro-oesophageal reflux disease [GORD], colic, constipation, diarrhoea
Skin symptoms: eczema, urticaria
Respiratoy symptoms

Screen for faltering growth
Measure weight, length/height, and calculation of body mass index (BMI)

Current feeding (bottle, breast, mixed)
Volume and frequency of feeding.
Form of the ingested milk (cow's milk protein in maternal breast milk, fresh, processed, cooked, or baked)
If the child is currently being breastfed, ask about the mother’s diet.
Any symptom response to dietary restrictions or cow’s milk reintroduction.

Personal or family history
Asthma, atopic eczema, and/or allergic rhinitis and food allergies.

Infants with a history of a severe allergic reaction, concurrent asthma, atopic eczema, or multiple food allergies, are at high risk for IgE-mediated cow’s milk allergy.

2. Identify and exclude Red Flag conditions

• Bile-stained vomiting

• Growth failure

• Developmental Delay

• Severe widespread eczema

• Blood in stools

Allergy testing

1. Allergy testing involves skin prick testing or measuring serum-specific immunoglobulin (Ig)E levels to cow's milk

2. Skin prick test sensitization may be suppressed by recent antihistamine, beta-blocker, tricyclic antidepressant (TCA), and topical corticosteroid use.

3. Allergy testing cannot distinguish between sensitization (presence of IgE antibodies but do not develop symptoms of clinical allergy) and ‘true’ clinical allergy,

4. Allergy testing may also be used to assess whether tolerance has developed: re-testing may be arranged every 12–18 months

5. If the results of allergy testing do not correspond with the clinical history, or the history is equivocal, an oral food challenge (baked or fresh cow's milk under medical supervision) in a supervised setting may be needed to confirm the diagnosis.

Management

1.Severe IgE-mediated allergy and/or anaphylaxis with or without angio-oedema

Arrange immediate ambulance transfer to Accident and Emergency

2. Suspected IgE-mediated cow's milk allergy

1. Refer to paediatric specialist allergy clinic for allergy testing to confirm the diagnosis
   Main aim is to diagnose severe IgE-mediated systemic reaction

2. Refer to a paediatric dietitian

3. Cow's milk-free diet options include:

   hypoallergenic infant formulas (extensively hydrolysed formula eHF; infant soy formula may be used of age>6m and NOT sensitised on IgE testing)
   exclude cow's milk protein from maternal diet for exclusively breastfed babies (but advise maternal calcium and vitamin D supplementation)
   substitute foods if complementary feeding (weaning)

4. If the infant is asymptomatic on exclusive breastfeeding, do not exclude cow's milk from the maternal diet

5. Screen food labels for milk protein
   Sodium caeinate, calcium caeinate, potassium caeinate, magnesium caeinate, protein hydrolysate, casein, milk serum, lactoalbumin, or lactoglobulin

6. If a diagnosis of IgE-mediated allergy is confirmed:
   Give written advice on prompt recognition and management of acute symptoms following exposure
   Use BSACI Allergy Action Plan to be used in home, childcare and school settings.
   If the child has a history of a severe IgE allergy or mild plus a history of asthma s/he should be prescribed an adrenaline pen.
   Oral antihistamines: mild/moderate allergic reaction (swollen lips/face/eyes, itchy tingling mouth, itchy skin rash, abdominal pain or vomiting)
   Auto-injector adrenaline: airway (cough, hoarse voice, swollen tongue), breathing (wheeze, difficulty breathing), consciousness (dizziness, collapse)

7. Follow up with specialist allergy clinic: serial interval IgE testing AND later planned supervised oral food challenge to test for acquired tolerance.

3. Suspected mild-to-moderate non-IgE-mediated allergy (most cases managed in primary care)

1. Establish diagnosis
   Trial elimination of all cow's milk protein from maternal/infant diet for for 2–4 weeks, to see if symptoms improve.
   Followed by,
   Trial of reintroduction of all cow’s milk protein, to see if symptoms recur, which CONFIRMS THE DIAGNOSIS

2. Allergy testing is not needed.

3. Advise cow's milk-free diet for the mother/infant until the child is 9–12 months old and for at least 6 months after confirmation of diagnosis

4. Refer to a paediatric dietitian

5. Cow's milk-free diet options include:

   hypoallergenic infant formulas (extensively hydrolysed formula eHF)
   exclude cow's milk protein from maternal diet for exclusively breastfed babies (but advise maternal calcium and vitamin D supplementation)
   substitute foods if complementary feeding (weaning)

6. If the infant is asymptomatic on exclusive breastfeeding, do not exclude cow's milk from the maternal diet

7. At age 9-12 months, if there is no current atopic eczema, no immediae onset symptoms, then, organise,
   planned HOME reintroduction of cow's milk protein into the mother/infant diet, to check if TOLERANCE has been acquired. Tolerance to cow’s milk protein should be checked every 6-12 months using a 'milk ladder' and monitoring for the return of symptoms. A milk ladder reintroduces baked milk products first as heating reduces allergenicity.

   However, if the child has current atopic eczema or immediate onset symptoms, DO NOT ADVISE HOME REINTRODUCTION and instead arrange referral to an allergy specialist to check serum specific IgE/ skin prick test and consider hospital supervised challenge.
   

4. Suspected severe non-IgE-mediated allergy (minority of cases)

1. Refer to specialist allergy clinic, if there is a history of faltering growth, severe non-IgE-mediated symptoms (gastrointestinal, skin with severe eczema), multiple food allergies

2. Refer to a paediatric dietitian

3. Cow's milk-free diet options include:

   hypoallergenic infant formulas (Amino Acid Formula, AAF)
   exclude cow's milk protein from maternal diet for exclusively breastfed babies (but advise maternal calcium and vitamin D supplementation)

4. If the infant is asymptomatic on exclusive breastfeeding, do not exclude cow's milk from the maternal diet

5. If severe non-IgE-mediated allergy AND/OR severe eczema, AND/OR gut symptoms, consider need to avoid soya protein and egg from the diet as well.

Hypoallergenic infant formulas

1. Extensively hydrolysed formulas (eHFs) are usually used first-line.
   eHF costs twice the price of regular formula (£130 per month).
   eHF is tolerated by 90% of infants with CMPA

2. Amino acid formulas (AAFs) should be reserved for children:
   With severe symptoms of IgE- or non-IgE-mediated allergy or a history of anaphylaxis.
   Who cannot tolerate or have ongoing symptoms with eHF.
   Breastfed infants whose symptoms do not respond to maternal avoidance of cow's milk

3. Soya protein-based formulas should not be used first-line.
   They contain appreciable amounts of isoflavones with a weak oestrogenic action
   Be aware that up to 60% of people with non-IgE-mediated cow's milk allergy and up to 14% with IgE-mediated allergy also react to soya.