Recognizing CMPA 

Case in point, continued: Within a few days of starting ready-to-eat infant formula, Ryan developed gastrointestinal (GI) symptoms, including vomiting and diarrhea, as well as mild eczema on the backs of his elbows and knees. His pediatrician suspected CMPA.

CMPA is one of the most common food allergies in children and is most prevalent in infancy, affecting 2% to 7% of all formula-fed infants.6,7The allergy is an immune response to the protein components of the casein and whey fractions of cow’s milk.6CMPA often presents during the first month of life and may develop in infants who are exclusively breastfed as a reaction to milk protein in the mother’s diet that is transferred through breast milk.6

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The reaction to cow’s milk protein may be immunoglobulin E (IgE)- or non-IgE-mediated.6An IgE-mediated reaction is an immediate (type 1) hypersensitivity reaction that usually occurs within 20 minutes and no more than 2 hours after exposure.6A non-IgE-mediated response is a delayed (type 4) reaction but can be severe nonetheless.6

Both IgE- and non-IgE-mediated reactions to cow’s milk protein produce cutaneous and GI symptoms 
(Table 2).6,7Symptoms of an IgE-mediated reaction are caused by histamine release and are temporally associated with ingestion of cow’s milk.6Typical symptoms include acute angioedema of the lips, tongue, and palate; oral pruritus, localized or general acute urticaria, and rhinorrhea.6 

Table 2.  Signs and symptoms of IgE-mediated and non-IgE-mediated allergy to cow’s milk protein.6

IgE-mediated Non-IgE-mediated
Skin Pruritus
Acute urticaria (localized or general)
Acute angiodema of lips, face, eye area
Atopic eczema
Gastrointestinal system Acute oropharyngeal angioedema
Oral pruritus
Colicky abdominal pain
Vomiting Diarrhea
Gastroesophageal reflux disease (GERD)
Loose or frequent stools
Blood or mucus in stools
Abdominal pain
Colic Food refusal or aversion
Respiratory system (usually in conjunction with other symptoms) Upper respiratory tract symptoms (eg, nasal itching, sneezing, rhinorrhea, congestion, conjunctivitis)
Lower respiratory tract symptoms (cough, wheezing, chest tightness, shortness of breath)
Lower respiratory tract symptoms (cough, wheezing, chest tightness, shortness of breath)
Other Signs of anaphylaxis or other systemic allergic reaction

A non-IgE-mediated, or T-cell-mediated, reaction presents with more chronic and nonspecific symptoms of pruritus and erythema, atopic eczema, gastroesophageal reflux disease (GERD), abdominal pain, colic or persistent crying, watery stools that may contain blood or mucus, and diarrhea.6,7

The pathophysiology of food allergy is complex and involves genetic, environmental, and prenatal and postnatal factors.8,9A family history of food allergy or other atopy is a strong risk factor for developing food allergies; children with asthma tend to have more severe allergic reactions to milk, particularly if the asthma is not well-controlled.6,7Maternal gestational diabetes, African-American race, and male gender are also associated with an increased risk for food allergy.8 

CMPA appears to be more prevalent among infants born by cesarean section compared with vaginal delivery and among infants born to mothers older than age 35 years at delivery.8On the other hand, factors that do not appear to increase the infant’s risk for CMPA include low socioeconomic status, maternal smoking, five or more previous deliveries by the mother, and multiple pregnancies on the part of the mother.8

The rate of parent-reported CMPA is about four times higher than the actual prevalence of the condition.10Parents frequently suspect CMPA when their child presents with such symptoms as cutaneous eruption, insomnia, persistent nasal obstruction, or seborrheic dermatitis. 

In some cases, parents will put their children on an unnecessary diet that may provoke nutritional imbalances, especially during the child’s first year of life. Thus, an accurate diagnosis of CMPA is required in order to avoid nutritional deficiencies that may lead to the child’s development of anemia, rickets, decreased bone mineralization, poor growth, anemia, and hypoalbuminemia.11

CMPA can be difficult to distinguish from nonallergic food problems.9Suspected CMPA should be evaluated by means of a thorough clinical history and by skin-prick test or measurement of blood levels of IgE to confirm IgE-mediated allergy.6,7,12 

If allergy tests fail to confirm the condition, 
a food challenge is the standard next step for diagnosis.6,12Both the skin-prick test and the food challenge should be performed in an allergy clinic or other facility capable of managing a rare but potential anaphylactic reaction.6

The only reliable test for diagnosis of non-IgE-mediated CMPA is that of a strict elimination diet.6Symptoms should improve within 2 to 4 weeks after milk exclusion; symptom improvement accompanied by recurrence of symptoms with the reintroduction of cow’s milk strongly suggests non-IgE-mediated CMPA.6 

With confirmation, the milk exclusion diet should be continued for at least 5 months or until the child reaches the age of 1 year, but only under clinical supervision to ensure adequate nutritional and caloric intake during exclusion and monitoring of any reaction during reintroduction.6,12