Intolerance of Cow's Milk and Chronic Constipation in Children. Iacono G, Cavataio F, Montalto G, Florena A, Tumminello M, Soresi M, Natarbartolo A, Carroccio A. N Engl J Med 1998;339:1100–4.
Iacono et al. hypothesized that intolerance to cow's milk can cause severe perianal lesions with pain on defecation and subsequent constipation in young children. They conducted a double-blind crossover study comparing cow's milk with soy milk in 65 children (age range, 11 to 72 months) with chronic constipation refractory to laxatives. Forty-nine had anal fissures and perianal erythema or edema. After 15 days of observation without dietary restrictions, the patients were randomly assigned to two groups. One group received cow's milk and the other soy milk for 2 weeks. To ensure that the children did not receive any other kind of milk or milk-containing foods during the study periods, all parents were given a list of the most common milk-containing foods to be avoided. The feedings were reversed after a 1-week washout period, during which the diet was unrestricted. Forty-four (68%) of the children responded while receiving soy milk, defined as eight or more bowel movements during a treatment period. Anal fissures and pain with defecation resolved. The response was confirmed with a double-blind challenge with cow's milk. None of the children who received cow's milk had a response. Children with a response had a higher frequency of coexistent rhinitis, dermatitis, or bronchospasm than those with no response (11 of 44 children vs. 1 of 21, P = 0.05). They were also more likely to have anal fissures and erythema or edema before the study (40 of 44 vs. 9 of 21, P < 0.001), evidence of inflammation of the rectal mucosa on biopsy (26 of 44 vs. 5 of 21, P = 0.008), and signs of hypersensitivity, such as specific IgE antibodies to cow's milk antigens (31 of 44 vs. 4 of 21, P < 0.001). The authors conclude that in young children chronic constipation can be a manifestation of intolerance to cow's milk.
Bottle-fed infants receiving cow's milk formula can have constipation, the extent of which is influenced by the composition and/or processing of the formula (Pediatrics 1999;103:E7). In infants between the ages of 6 and 12 months cow's milk does not seem to cause more constipation than cow's milk–based formula (J Pediatr 1987;111:813–6). It is unlikely that all infants who are constipated while fed cow's milk have intolerance to cow's milk. However, it is plausible that a subgroup does.
The clinical manifestations of immunoglobulin (Ig)E–mediated (type I) cow's milk protein–induced allergy include: gastrointestinal symptoms with vomiting, diarrhea, shock and enterocolitis; atopic eczema; bronchitis and asthma; rhinitis; eosinophilic gastroenteritis; and possibly infantile colic. The onset is immediate, within up to 1 hour after ingestion. The onset of non-IgE–mediated reactions (type III or IV) is intermediate (1–24 hours) or late (>24 hours). The clinical manifestations include enteropathy with diarrhea and malabsorption, eosinophilic colitis, protein-losing enteropathy, and intractable diarrhea of infancy (Rudolph's Pediatrics. London: Prentice Hall International, 1996:1100–1).
The present report suggests that constipation is an additional symptom of cow's milk intolerance. A case of chronic constipation as the sole symptom of intolerance to cow's milk had been described earlier in a 2.5-year-old boy (BMJ 1983;287:1593). However, constipation was not a clinical feature in a series of 53 children with allergic proctitis (15 patients) and allergic gastroenteritis (38 patients) (Am J Surg Pathol 1986;10:75–86). In four newborns with constipation (age range, 7 days to 5 weeks) who underwent rectal biopsies to exclude Hirschsprung disease, ganglion cells were demonstrated as well as evidence of allergic colitis. Symptoms resolved after removal of milk from the diet (Pediatr Radiol 1999;29:37–41). In all patients, the initial radiologic findings suggested Hirschsprung disease.
Most infants with allergic colitis have the onset of disease within the first few months of life and can tolerate milk by 1.5 to 2 years of age (J Pediatr 1995;126:163–70). The patients in the present study are older. It would be interesting to know whether they also will develop tolerance to cow's milk later in life. Up to 30% of infants sensitive to cow's milk protein are also sensitive to soy proteins (J Pediatr 1995;126:163–70). It may be that in the present study patients who did not improve while receiving soy milk were sensitive to both and would improve on diets without cow's milk and without soy protein. The finding of eosinophils in stool samples stained with Wright stain is suggestive of allergic colitis (J Pediatr 1995;126:163–70). It would be interesting to know whether that is also the case in the patients found to be intolerant of cow's milk in the present study.
In young children with chronic constipation, intolerance to cow's milk should be considered. The ages at which it should be considered as well as the optimal evaluation establishing the diagnosis remain to be defined further.