ABM Clinical Protocol #24: Allergic Proctocolitis in the Exclusively Breastfed Infant

Incidence

The incidence of adverse reactions to food proteins in the exclusively breastfed infant is poorly defined. Prospective data indicate approximately 0.5–1% of exclusively breastfed infants develop allergic reactions to cow’s milk proteins excreted in the mother’s milk. Given that cow’s milk protein is the offending antigen in 50–65% of cases, the total incidence of food allergy in the exclusively breastfed infant appears slightly higher than 0.5–1%. Comparatively, infants fed human milk appear to have a lower incidence of allergic reactions to cow’s milk protein than those fed cow’s milk–based formula. This may be attributable to the relatively low level of cow’s milk protein excreted in human milk, immunomodulatory substances present in human milk, and/or differences in the intestinal flora between breastfed and formula-fed infants.

Clinical presentation

The most common symptoms associated with food-induced allergic disorders in the exclusively breastfed infant are cutaneous reactions (eczema) and gastrointestinal symptoms. Severe manifestations of food allergy are extremely rare. The most common gastrointestinal symptom is the development of bloody stools. This usually occurs between 2 and 6 weeks of age, although some have reported symptoms beginning as early as the first day of life. Dietary proteins excreted in the mother’s milk are responsible for the majority of cases and induce an inflammatory response of the rectum and distal sigmoid colon referred to as allergic proctocolitis. It should be emphasized that breastfed infants with allergic proctocolitis are generally “well appearing” other than the presence of blood within the stool. Blood loss is typically modest but can occasionally produce anemia and/or hypoalbuminemia. In very rare cases, symptoms may lead to failure to thrive. Systemic manifestations such as emesis, dramatic diarrhea, or abdominal distention are rare and may suggest other allergic disorders of the gastrointestinal tract such as food protein–induced enterocolitis or enteropathy (not reviewed in this protocol).

Additional laboratory studies may be considered but are often unnecessary to make the diagnosis of allergic proctocolitis. Peripheral eosinophil counts may be elevated; however, this is poorly indicative in an individual patient. A fecal smear looking for an increased number of eosinophils is often reported negative. If the fecal smear does not contain detectable leukocytes, it is not suitable for mucosal cytology, and the report of no eosinophilia is not reliable (T. Takamasu, personal communication, June 9, 2011). Stool cultures are negative for pathogenic bacteria, and radiographic studies exclude necrotizing enterocolitis. Total and antigen-specific serum immunoglobulin E concentrations are similar to those of non-affected infants and thus need not be measured. In severe or protracted cases unresponsive to dietary modification, endoscopic evaluation may be warranted.

Pathophysiology

The symptoms and severity of food hypersensitivity vary according to the mechanism of immune response (immunoglobulin E vs. cell-mediated) and location of intestinal involvement. Allergic proctocolitis in the breastfed infant is a cell-mediated hypersensitivity disorder of the distal large bowel characterized by mucosal edema, focal epithelial erosions, and eosinophilic infiltration of the epithelium and lamina propria. Biopsy specimens typically demonstrate eosinophil counts of greater than 20 per high-powered field. The passage of dietary proteins into maternal milk is responsible for the majority of cases, and elimination of the offending agent from the maternal diet usually results in cessation of symptoms within 72–96 hours. In some cases, dietary restriction for up to 2–4 weeks may be required to notice improvement. In a published series of 95 breastfed infants with bloody stools, 65% were determined to be attributable to maternal ingestion of cow’s milk, 19% to egg, 6% to corn, and 3% to soy.

It remains unclear when the sensitization phase of allergic proctocolitis occurs. Some infants have been reported to respond adversely to food proteins excreted in the mother’s milk within the first day of life. It is apparent that dietary and environmental antigens are capable of crossing the placental barrier or entering the amniotic fluid, which is swallowed by the fetus. These findings suggest the possibility of in utero sensitization following maternal antigen exposure during pregnancy. Alternatively, variations in the concentration of several immunomodulatory substances in human milk appear to influence the protective effect of breastfeeding against allergy. Human milk contains viable leukocytes that may play a role in antigen processing and presentation to neonatal lymphocytes in the intestine. Thus, it is possible that ingestion of dietary food proteins excreted in the mother’s milk, accompanied by physiologic conditions favoring immunogenic responses (in the neonate or maternal milk), may result in allergic sensitization. At present, however, there are insufficient data to recommend dietary restriction during pregnancy and/or lactation as a means of allergy prevention. Breastfeeding should be encouraged in all neonates, even though small quantities of food allergens may be present within the milk. Indeed, recent data in animal models suggest that ingesting small quantities of allergens excreted in the mother’s milk in the presence of the anti-inflammatory cytokine transforming growth factor-b may actually protect offspring against subsequent allergic responses to that same allergen later in life.