Milk Protein Intolerance

A number of food-associated disorders of the GI tract are included in this diagnosis. A variety of food protein antigens can be implicated, with milk protein ibeing the most common historically, and any part of the GI tract can be involved, from esophagus to rectum. The disorder is classified into either IgE mediated, non-IgE mediated, or mixed. 



An orally ingested protein produces an inflammatory response early on in infants. Interestingly, a large portion of these infants are breastfed and this occurs less commonly in cow’s milk or soy based formula fed children. 

In the IgE mediated case, there will be a predominance of esoinophils in the mucosal layer. In non IgE mediated case, there is a cell mediated inflammatory response to the offending food, with some evidence that TNF-alpha is released by T-Cells in response to the food antigen. In general, the mechanism is poorly understood, but the basic idea boils down to an inflammatory reaction to a certain “food antigen.”

Typical Offending Foods: Cow’s milk for “Milk Protein Intolerance,” but other common early childhood food antigens include egg, soy, peanuts, tree nuts, wheat, fish, and shellfish.



IgE Mediated Symptoms

  • GI: Gastrointestinal symptoms
  • Cutaneous: Uticaria, angioedema
  • Respiratory: Acute asthma, acute conjunctival symptoms

Non IgE Mediated Symptoms

  • GI: Proctocolitis and enterocolitis
  • Cutaneous: Contact dermatitis
  • Respiratory: Food-induced pulmonary siderosis

Mixed Pattern:

  • Can include eosinophilic esophagitis


Clinical Presentation

Food Protein Induced Enterocolitis should be considered in generally healthy infant who presents with blood-tinged stool. The presence of mucous suggests “protein induced proctocolitis”

Some infants may exhibit fussiness and increased frequency of stool, but usually not diarrhea

Presentation usually at 2-8 weeks of age.

A more severe form is “protein induced enterocolitis syndrome,” which includes diarrhea, vomiting, failure to thrive, and malabsorption.


Differential diagnosis

  • Anal Fissure
  • Intussusception
  • Colic
  • GERD
  • Meckel’s Diverticulum


Making the diagnosis

The diagnosis is made retrospectively when the clinical presentation resolves upon the withdrawal of the supposed food antigen. In some cases, a medically supervised food challenge can be done to observe the association of food antigen and clinical symptoms, yet the utility and safety of this assessment is controversial.

If the infant has persistent bloody stools despite strict elimination of the presumed antigen, more invasive testing such as colonoscopy should be considered to investigate for alternative pathology. Skin prick allergy tests are not helpful in the diagnosis of of food protein induced enterocolitis because it is a non IgE mediated process.



Mothers of exclusively breast fed infants should eliminate all dairy products including butter from their diet. Then, they are asked to continue breast feeding once diet elimination has taken place.

Formula fed or supplemented infants must be switched to protein hydrolysate formulas, switching to soy based does not solve the problem. The new formula should be “Hydrolyzed Casein” or “Amino Acid Based”

With proper elimination, bleeding should resolve within 72 hours, persistent symptoms warrants further investigation

Reintroduction of cow’s milk or soy based formulas should not be done before six months of age. However, reintroduction can be started after 6 months.



Most infants will be able to tolerate the previously antigenic protein between one and two years of life as it is largely a self-limiting disease process. Although uncommon, hypersensitivity reactions can linger in a subset of children and take longer to resolve.



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  2. Vandenplas, Yvan, et al. Guidelines for the diagnosis and management of cow’s milk protein allergy in infants. Archives of disease in childhood 92.10 (2007): 902-908.
  3. Cherry, Rebecca, and Dan W. Thomas. Infant feeding in special circumstances. Pediatrics in Review 29.8 (2008): 274-280.
  4. Leonard SA, Nowak-Wegrzyn A. Food protein-induced enterocolitis syndrome: an update on natural history and review of management. Ann Allergy Asthma Immunol. 2011 Aug; 107(2): 95-101
  5. Nowak-Wegrzyn, Anna, et al. Food protein-induced enterocolitis syndrome caused by solid food proteins. Pediatrics 111.4 (2003): 829-835.