Infantile cow’s milk protein allergy (CMPA) (J. Robert*)

T6, 07/11/2014 - 15:15
allergies au lait de vache du nourrisson  Dr Robert

*Dr. J. Robert - Pediatrician - Atopic Dermatitis Therapeutic Education Consultation - Lyon Sud Hospital Center - Pavillon Dufour - 69495 Pierre Bénite Cedex

Cow’s milk protein allergies (CMPA) affect 2 to 3% of infants. They appear when weaning or when giving the first bottles of milk. The allergy causes cutaneous, digestive or more rarely respiratory symptoms. Their onset depends on the underlying immunopathological mechanism, which makes a didactic classification and practical exploration of the allergic reactions possible.


  1. The immediate manifestations are IgE-mediated

They are obvious and appear rapidly, in the minutes or hour following the bottle’s ingestion. The clinical picture can combine any of the following:

  • rapid vomiting (and not simply regurgitation) that is repeated if ingestion continues
  • explosive diarrhea
  • acute urticaria, angioedema (a deep facial urticaria)
  • pallor, malaise, anaphylactic shock
  • proctorrhagia, rare but characteristic of young infants
  • asthma attack.
  1.  Non-IgE-mediated manifestations

They are less clearly defined, take longer to manifest themselves, are cell-mediated or immune complex and are consistent with its former name of milk intolerance (CMPI):

  • For the clinician, a vague symptomatology can include: crying, irritability, sleep disorders, refusal to eat, repeated vomiting, sometimes bloody recurrent diarrhea, bloating, constipation and weight stagnation.
  • A pediatric gastroenterologist will speak of allergic enterocolitis, enteropathy and allergic colitis.
  1. Mixed diseases: IgE-mediated and non-IgE-mediated

The recently described eosinophilic diseases (oesophagitis, gastritis, colitis) involve a painful reflux symptomatology that reacts poorly to PPIs, a feeling of satiety after ingesting small doses, persistent colic beyond the age of 3 months and a malabsorption syndrome with chronic diarrhea. There is nothing specific, and we find the same signs as those described in non-IgE-mediated manifestations. Faced with these clinical forms, the pediatric gastroenterologist may propose a fiberoptic endoscopy and biopsy.

The eczema and CMPA combination remains a subject of controversy. For practical and consensual reasons, let us stick to the facts:

  • Infants with atopic dermatitis are more prone to developing a food allergy than those not affected by this condition.
  • The earlier the atopic dermatitis appears, the more severe the condition and the harder it is to treat, the more it makes sense to test for an associated CMPA capable of making the lesions worse, even when the specific IgE test is negative, since this is a non-IgE form.
  • If the atopic dermatitis is combined with digestive complaints, or with weight stagnation, such a test is essential. A check-up is not required in cases of “naked” atopic dermatitis with no associated signs.
  • Documented clinical and paraclinical arguments are required before removing cow’s milk from the diet of an infant with eczema. You cannot just stop it “to see”.


First-line examinations must include skin tests, because they are easily carried out by all doctors, they are painless and they are safe.

  1. The skin prick test is used to diagnose IgE-mediated reactions. It can be carried out in the first weeks of life using the milk the baby is drinking. At this age, babies are not very sensitive but display very specific signs. The skin is pricked through a drop of milk placed on the forearm. Tap water is used as a control drop. The reaction is positive if you see a papule within 15 minutes measuring at least 3 mm, and if the control is negative.
  2. The patch test is used to study delayed-type reactions. It consists in placing the allergen (milk powder) in contact with the skin for 48 hours. A standardized, ready-to-use patch (Diallertest®) can be found in pharmacies. It contains small peptides like those released in the intestine after digestion. The patch is left for 48 hours, then the doctor must read the result vs. the control patch on day 3. In digestive forms and in case of atopic dermatitis, it is best to combine both types of test (prick and patch). You can establish a relationship between the atopic dermatitis and a cow’s milk protein allergy if after 72 hours the doctor can read and feel (with his finger) a papule and sometimes a vesiculation. This means that milk is an aggravating factor for the atopic dermatitis.
  3. Elimination/reintroduction tests are the reference. The doctor may recommend elimination, and reintroduction will take place in a hospital environment. For this, the child will use a hydrolyzed milk, called EH milk. Symptoms should improve rapidly in case of an acute form, but only after a few weeks if it is a non-IgE-dependent form. If it is combined with atopic dermatitis, the latter will improve, but not necessarily disappear! The skin must continue being treated...



Biological tests for specific IgE using the RAST method (Pharrmacia Cap System®) give results comparable to skin prick tests and are requested: if tests come back negative unexpectedly and in contradiction with the clinical history; if there is no interval during which the test can be carried out on healthy skin; or if the child is taking antihistamines. Ask for: RAST cow’s milk (f2) and casein (f78).

Exploration of intestinal mucosa: faced with any form of inflammatory lesion (from oesophagitis to proctitis), an eosinophilic infiltrate is very evocative of an allergic mechanism (tested for at the hospital after an endoscopy and biopsy). The double-blind oral provocation test is considered by some to be the “gold standard” of any food allergy. But:

  • it is not necessary if the allergy is immediate, as mother and baby have just proven!
  • it may be considered in cases of eosinophilic gastroenteritis, but the milk will need to be given over several days, after elimination, to trigger the clinical picture.


Treatment consists exclusively of eliminating cow’s milk protein and derivatives. The milk is replaced by an extensively hydrolyzed substitute (EH milk) available in pharmacies and (mostly) paid for by medical insurance.

In case of allergy to extensively hydrolyzed protein (rare), or if the signs persist with severe eczema and growth retardation, a formula containing free amino acids is indicated.

The following are not suitable for managing an allergy to cow’s milk protein: other milks of animal origin (goat, sheep, mare, ass) due to cross-reactions; hypoallergenic formulas (partial hydrolysis); and “milky” almond, soy or chestnut-based drinks (calcium and protein deficiency and risk of sensitization). In these hydrolyzed milks, the milk protein is “diluted” so it is no longer allergenic. Several brands exist. Medical-prescription rice hydrolysates have more recently been marketed that are also suitable for allergic infants, and are thought to be well tolerated in 90% of cases.

Possible prevention: probiotics. In case of a cow’s milk protein allergy combined with atopic dermatitis, better results are thought to be obtained if lactobacilli (strain GG) or bifidus (strain Bb-12) is added to a diet of EH milk or Neocate.



Cow’s milk protein allergies (CMPA) are easily diagnosed from a clinical viewpoint in cases of acute IgE-dependent forms. They can be satisfactorily confirmed by simply pricking the skin through a drop of milk.
Enteropathic forms of cow’s milk protein allergies (CMPA) are harder to diagnose. In this case, an elimination test is preferred.

It is in groups of infants with eczema that most food allergies are discovered, compared to control groups with healthy skin.

But in order to accuse a cow’s milk allergy of triggering eczema or making it worse, you need strong arguments:

  • In this case, the atopic dermatitis is not “naked” and resists to the correct treatment.
  • A patch test induces a nummular eczema reaction after 72 hours.
  • Eliminating milk protein improves the child’s condition.



Breuer K, Heratizadeh A, Wulf A et al. Late eczematous reaction to food in children with atopic dermatitis. Clin Exp Allergy 2004; 34: 817-824
DUPONT C et al. Prise en charge diététique de l’allergie aux protéines du lait de vache. Arch Pediatr 2011 ;18 : 79-94
DUTAU G. Dictionnaire des allergènes 1vol 2007. Phase 5 Ed.
SAMPSON HA. Update on food allergy. J Allergy Clin Immunol, 2004, 113: 805-819.