Cow’s milk protein/allergy intolerance

A common issue for babies and infants.  “Intolerance” suggests that cow’s milk causes adverse effects(not specified, but generally gastrointestinal) but without committing to an underlying mechanism. 

If there is reason to think the adverse effects are immune mediated (because there are signs/symptoms outside the GI tract, for example) then it is preferable to use “cow’s milk allergy” (which then divides into type 1, non type 1, or mixed). 

Can even affect exclusively breast fed infants if sufficient milk proteins transmitted in breast milk.

Not the same as lactose intolerance – lactose is a sugar, intolerance to it is due to malabsorption and effects of undigested sugar in colon eg bloating, diarrhoea.  NOT rash, vomiting.  Usually post-gastroenteritis, transient.  No useful test other than lactose restriction for 2 weeks then rechallenge.

Cow’s milk allergy

Can be IgE mediated (immediate, histamine release, potentially anaphylaxis), else non-IgE mediated (typically more chronic, delayed symptoms, predominantly gastrointestinal, possibly a threshold level below which a patient is asymptomatic) but can be both. Non-IgE mediated symptoms include:

  • Eczema
  • Colic
  • Gastro-oesophageal reflux
  • Constipation
  • Eosinophilic oesophagitis
  • Enterocolitis
  • Proctocolitis
  • Growth failure

Note that the first 4 problems are very common and cow’s milk protein intolerance may only be a factor in a small proportion of such patients.

In patients with eczema, a mixture of IgE mediated and non-IgE mediated reactions can be seen (and immediate reactions may be seen on re-introduction even when only delayed reactions seen initially).


With delayed reactions, diagnosis depends on history, and then dietary exclusion followed by re-challenge after 2-4 weeks. In the case of FPIES, re-challenge may need to be done in hospital. Sometimes the diagnosis is only made at endoscopy.

For immediate reactions, skin prick testing (SPT) more specific than IgE blood testing. 3mm SPT wheal considered positive in infants; when doing IgE/SPT tests, also check egg allergy (high cross-reactivity) and soy (for formula substitution). If IgE/SPT negative, needs challenge (ideally double blind).

Substitute Formulas

  • Breast feeding mothers may need to exclude dairy in their own diet.  Need supplements of 1000mg calcium, 10mcg vit D per day
  • Because of theoretical risk from phyto-oestrogens in soya, use extensively hydrolysed formula (EHF) instead of soya formula if under 6 months. Soya cross reactivity seen in 25% of young infants, only 5% of over 6 months. Soya milk usage is also associated with increased risk of subsequent peanut allergy (RR=2.6)!
  • About 10% of infants will not tolerate even extensively hydrolysed formula and may require an amino acid based formula; anaphylaxis has been described even with hydrolysed formula.  AA formula should be used first line if:
    • anaphylaxis,
    • severe non IgE (eg PR bleeding leading to haematological disturbance, severe skin disease, FPIES),
    • faltering growth.
  • eHF potentially better than other types of feeding, and potentially added benefit from probiotics – in trial of N=260 (42% IgE mediated, non-randomised) tolerance after 12 months 79% for EHF & Lactobacillus rhamnosus GG (LGG), cf 43% for EHF. 23% soya, 18% AA. Associated with IgE mechanism (negatively, OR 0.12), and EHF (4.41) or EHF & LGG (29) [Canani, European lab for food induced diseases, Naples. PMID 23582142].

Reintroduction – cow’s milk must be reintroduced to prove it is the causal agent.  If symptoms return then continue elimination diet for at least 5 months, else 1yr of age.


Exposure does encourage tolerance. In studies, after 6 months of oral desensitization, 11% had had positive food challenges cf 40% for abstainers. And in the abstainers, the threshold of sensitivity tended to be lower, and symptoms more severe [Eur Ann Allergy Clin Immunol. 2007 39:12-9. PMID 17375736].

IgE disease less likely to resolve if asthma, rhinitis, severe reactions or strongly positive results.  Median age of tolerance 5yrs.  But consider risk of co-sensitivity esp egg allergy. According to Thermofisher, positive IgE Casein (Bos d 8) means less likely to tolerate baked milk or outgrow, as protein (casein) more heat stable.

For non-IgE disease, most resolve by age 2.5yrs.


See EAT study, and GINI study.


66% of kids grow out cow’s milk allergy, even if they completely avoid it. But rate rises to nearly 90% if baked milk introduced. And less restrictive diet good for everyone, of course.

16x more likely to tolerate fresh milk with baked milk immunotherapy compared with avoidance but significant anaphylaxis rate. Important for older kids (3yrs+).

Oral immunotherapy (OIT) for severe milk allergy (IgE >85 or low eliciting dose):  at 1 yr 36% tolerated 150ml, 54% 5-150ml (good enough for accidental exposure). 10% could not complete protocol.

5% of kids who had OIT for milk, egg or peanut developed eosinophilic oesophagitis, so this should probably be considered a possible complication.

Sublingual immunotherapy (SLIT) for milk? Low rate of success and high rate of relapse

[Frontiers in Pediatrics 2019; BMJ cmpa article sept 2013]