Lymphoid Nodular Hyperplasia and Cow’s Milk Hypersensitivity in Children with Chronic Constipation

Turunen S, Karttunen TJ, Kokkonen J. J Pediatr. 2004; 145:606–611 Purpose of the Study. To investigate the incidence of cow’s milk allergy as evidenced by milk challenge and the findings of endoscopic and immunohistochemical examinations in children with chronic and refractory constipation. Study Population. Thirty-five children aged 3 to 15 years with recalcitrant constipation and 15 control subjects. Methods. All children underwent colonoscopy with visual inspection for lymphoid nodular hyperplasia. Mucosal samples were taken from the terminal ileum, cecum, transverse colon, and rectum. Biopsy specimens were evaluated for the presence of lymphoid nodules, lamina propria eosinophils, and mononuclear cells. Immunohistochemical staining was done for CD3 T cells, and T-cell receptor–bearing intraepithelial lymphocytes, and HLA-DR expression. Subjects were placed on a 4-week milk-elimination diet. Other recommendations included a fiber-rich diet and medical treatment with lactulose and sodium picosulfate. For those who responded to elimination, milk was used as a challenge in the ensuing 4-week period. Total serum concentrations of IgA and IgE were measured. Results. Lymphoid nodular hyperplasia was the most prominent endoscopic finding and was detected in 46% of subjects. During the period of milk elimination/supportive medication, 83% of subjects remitted. Relapse occurred in 34% of children after challenge with milk. These children had significantly higher densities of intraepithelial T cells (P .001) in biopsy samples from the terminal ileum. Conclusions. The authors concluded that these results indicate formal evidence of cow’s milk allergy in children with chronic constipation. Reviewer’s Comments. It is fairly common that parents blame cow’s milk formulas for constipation. This study showed that a subset of children (those with higher densities of intraepithelial T cells in the terminal ileum) whose constipation improved with a regimen that included cow’s milk avoidance had a relapse of constipation when reexposed to cow’s milk. These results are intriguing and suggest an immunologic link but do not provide formal evidence of cow’s milk allergy. Proof of cow’s milk hypersensitivity would require demonstration of specific recognition of cow’s milk protein by the immune system.