Picture this: A 6-month-old little champ, seemingly struggling with tummy troubles, skin woes, and a reluctance to feed. His concerned parents, noticing frequent vomits after feeds and a concerning weight loss, are at their wit’s end. Amidst a whirlwind of potential diagnoses, there’s one that takes the spotlight: Cow’s Milk Protein Allergy (CMPA). Let’s delve into this intriguing medical mystery, exploring the signs, symptoms, and solutions surrounding this top contender on the list of possible culprits.

Cow’s milk allergy is a reproducible immune-mediated allergic response to one or more proteins in cow’s milk. It is one of the most common presentations of food allergy seen in early childhood, second to egg allergy. 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 with a lower incidence in exclusively breast-fed babies. Most children will outgrow this condition by 6 years of age.

Classification and pathophysiology

Cow’s milk contains more than 20 protein fractions. The significant allergens belong to casein protein and whey proteins. Most individuals with cow’s milk allergies have a sensitivity to both caseins and whey proteins.

Like any other food allergy, CMPA can be either IgE mediated or non- IgE mediated:

• IgE mediated food allergy follows exposure and sensitization to allergen(s) with the development of serum-specific IgE antibody. It produces immediate and consistently reproducible symptoms which may affect multiple organs systems. Reactions typically occur up to 2 hours after cow’s milk protein ingestion, usually within 20–30 minutes. (IgE = Immediate)
• Non-IgE-mediated food allergy involves a cell-mediated mechanism and reactions are typically delayed. They usually manifest between 2 and 72 hours after cow’s milk ingestion.( Non IgE = Not Immediate= delayed)
• Mixed IgE and non-IgE allergic reactions involve a mixture of both IgE and non-IgE responses and are typically delayed.

Risk Factors:

• Male sex — boys have a two-fold higher risk of developing cow’s milk allergy than girls in childhood.
• Known food allergy — the presence of a confirmed food allergy increases the likelihood of additional food allergies.
• Other atopic conditions, such as asthma and atopic eczema.
• Family history of food allergy — confirmed food allergy in a parent or sibling increases the risk of food allergy.
• Family history of atopy.
• Breast-fed babies have a lower chance of developing CMPA or food allergies.

Clinical presentation and diagnosis:

Faltering growth is a rare sign of CMPA and should go with a prolonged history of untreated CMPA. If there is a history of faltering growth / failure to thrive treat this as a red flag and exclude other more serious diagnoses first, e.g. infection, cystic fibrosis

Management:

History

• Ask about age of first onset, speed of onset and severity following milk ingestion. Also ask about previous management including medication use and response.
• An allergy-focused clinical history is the cornerstone of the diagnosis. A history of eczema, asthma, hay fever, allergic rhinitis or food allergy is more likely in IgE-mediated food allergy

Non-IgE mediated CMPA

1. Advise a trial elimination of cows’ milk for a period of 4-6 weeks

Symptoms do not improve (and exclusion has been adhered to)

It is important to inform parents that a clear improvement of CMPA symptoms is usually noticeable after the exclusion of cow’s milk protein in 2 to 4 weeks.

2. Re-challenge to confirm the diagnosis of Non-IgE-mediated cows’ milk protein allergy (after 4-6 week exclusion)

• If the infant is exclusively breastfed introduce cows’ milk back into the diet of the mother.
• If the child is formula or mixed-fed reintroduce cows’ milk formula.
• If the child has been weaned onto solid foods, then reintroduce cows’ milk into the diet and return to cows’ milk-based formula.

3. Ongoing management of non IgE-mediated cows’ milk protein allergy

• Strict avoidance of cows’ milk protein for at least 6 months or until the child is 9-12 months old and evaluate the child every 6 months.
• Seek advice from a paediatric dietitian for guidance on nutritional adequacy and re-introduction of milk protein (milk ladder).

IgE-mediated CMPA

Consider a cows’ milk specific IgE antibody test, only after taking an allergy focused clinical history.

• Total exclusion of cows’ milk from diet.
• Cows’ milk replacement. Extensively Hydrolysed Formula as first-line for mild to moderate IgE-mediated CMPA. (Similac Alimentum, Aptamil Peptijunior, or nuntramigen)
• Consider Amino Acid Formula (AAF) if severe CMPA. (SMA Alfamino)
• Make parents aware of the possibility of an anaphylactic reaction, when and how to seek urgent medical help.

Every hospital / CCG will have different brands of hydrolysed or amino acid formulas that are their first line, if you’re not sure just ask. It’s also worth noting that hydrolysed formulas taste disgusting and babies started on this will often have some spitting up to begin with and may even feed less.

Lactose intolerance: an important differential

Lactose intolerance is another type of reaction to milk, when the body cannot digest lactose. However, this is not an allergy.

Lactose intolerance can be temporary – for example, it can come on for a few days or weeks after a tummy bug. It is rare in babies and tends to affect toddlers and older children

Symptoms of lactose intolerance include:

• diarrhoea
• vomiting
• stomach rumbling and pains
• wind

Other differentials to bear in mind:

• Gastro-oesophageal reflux Will present with crying after feeds, particularly when laid flat +/- vomiting, should not have bloody stools
• Coeliac disease Tends to affect older children and presents with failure to thrive, loose and offensive smelling fatty stools, wasting of buttocks
• Gastroenteritis Short history of vomiting with loose stools and history of contact with other people with gastroenteritis
• Urinary tract infections In a grumpy, vomiting baby
• Cystic fibrosis Will also present with failure to thrive, recurrent chest infections
• Non-CF- related pancreatic insufficiency Will present with loose fatty stools and failure to thrive
• Intussusception Would present in a similar way to CMPA with a grumpy baby, vomiting and bloody stools but will very short and sudden onset of history and baby will be clinically more unwell. Blood in stool resembles “redcurrant jelly”

The allergyuk.org website has a lovely resource to share with parents

Happy Learning!

Written by Dr. Afreen Mushtaque

Edited by Dr Rebecca Evans Paediatric Registrar