Colonic Crohn's disease in children does not respond well to treatment with enteral nutrition if the ileum is not involved.

Data supporting a response to treatment with exclusive enteral nutrition in pediatric colonic Crohn's disease are few. We examined clinical and biochemical responses of ileal, colonic, and ileocolonic Crohn's disease and assessed the endoscopic and histological colonic mucosal response in the colonic and ileocolonic groups. We prospectively enrolled 65 children (age: 8-17 years) with acute intestinal Crohn's disease (Pediatric Crohn's Disease Activity Index [PCDAI] >20). After ileocolonoscopy, gastroscopy, and a barium meal and follow-through, they were distributed into three groups (ileal, n = 12, ileocolonic, n = 39; and colonic, n = 14). All patients received exclusive polymeric feed as treatment, with a repeat endoscopy at completion of treatment. At enrollment the ileal group had significantly less severe disease (P = 0.05) compared to the colonic and ileocolonic groups. However, the colonic disease group showed the least fall in PCDAI scores at completion of treatment with enteral nutrition (P = 0.03), with the lowest remission rate (50%, vs 82.1% in the ileocolonic and 91.7% in the ileal group [chi2 test, P = 0.021]). Endoscopic and histologic colonic mucosal assessment showed a post-treatment improvement in the ileocolonic (P < or = 0.01) but not in the colonic disease group (P = ns). Children with disease in the colon respond better to enteral nutrition if the ileum is also involved. This may be due to different underlying inflammatory mechanisms. Detailed pretreatment assessment in studies of Crohn's disease according to disease distribution with appropriate individualized tailoring of treatment may be important in this regard.

Intestinal lymphocyte populations in children with regressive autism: evidence for extensive mucosal immunopathology.

Inflammatory intestinal pathology has been reported in children with regressive autism (affected children). Detailed analysis of intestinal biopsies in these children indicates a novel lymphocytic enterocolitis with autoimmune features; however, links with cognitive function remain unclear. To characterize further, the nature and extent of this disease we examined the mucosal infiltrate using flow cytometry. Duodenal, ileal, and colonic biopsies were obtained from 52 affected children, 25 histologically normal, and 54 histologically inflamed, developmentally normal controls. Epithelial and lamina propria lymphocyte populations were isolated and examined by multicolor flow cytometry. Adjacent biopsies were assessed by semiquantitative histopathology. At all sites, CD3(+) and CD3(+)CD8(+) IEL as well as CD3(+) LPL were significantly increased in affected children compared with developmentally normal noninflamed control groups (p<0.01) reaching levels similar to inflamed controls. In addition, two populations--CD3(+)CD4(+) IEL and LP CD19(+) B cells--were significantly increased in affected children compared with both noninflamed and inflamed control groups including IBD, at all sites examined (p<0.01). Histologically there was a prominent mucosal eosinophil infiltrate in affected children that was significantly lower in those on a gluten- and casein-free diet, although lymphocyte populations were not influenced by diet. The data provide further evidence of a pan-enteric mucosal immunopathology in children with regressive autism that is apparently distinct from other inflammatory bowel diseases.

Reduced transforming growth factor-beta1-producing T cells in the duodenal mucosa of children with food allergy.

Infant food allergies are increasing, and many breast-fed infants now sensitize to maternally-ingested antigens. As low-dose oral tolerance requires generation of suppressor lymphocytes producing TGF-beta1 (Th3 cells), we studied these cells in duodenal biopsies after diagnostic endoscopy. Spontaneous production of Th1, Th2 and Th3 cytokines by duodenal lymphocytes was studied using flow cytometry in 20 children with no eventual clinico-pathological diagnosis (controls), 30 children with multiple food allergy, nine with celiac disease and six with inflammatory enteropathies. Immunohistochemistry and in situ hybridization were used to localize TGF-beta1 protein and mRNA in matched biopsies. We found no significant Th1/Th2 skewing amongst mucosal lymphocytes in allergic children compared to controls, although celiac and inflammatory enteropathy patients showed increased Th1 responses. By contrast, the allergic children showed reduction of TGF-beta1(+) lymphocytes in both epithelial and lamina propria compartments. Reduction of TGF-beta1 expression was also seen in mononuclear cells and epithelium in food allergy by immunohistochemistry and in situ hybridization. The dominant mucosal abnormality in food allergic children was, thus, not Th2 deviation but impaired generation of Th3 cells. As generation of these cells requires innate immune response to enteric bacteria, we suggest that changing infectious exposures may inhibit primary establishment of basic oral tolerance mechanisms.

A consistent pattern of minor immunodeficiency and subtle enteropathy in children with multiple food allergy.

OBJECTIVE: Although immunoglobulin (Ig)E-mediated allergies are readily identifiable, non-IgE-mediated allergies present more diagnostic difficulty. We performed a formal retrospective analysis to determine whether there is a recognizable clinical pattern in children. METHODS: We studied 121 children (mean age, 17.3 months) with multiple food allergies who were recruited on the basis of adequate immunological assessment by using case notes and parental questionnaire. RESULTS: Group 1 (n=44) had rapid reactions to dietary antigens, of whom 41 also showed delayed reactions. Group 2 (n=77) had delayed reactions only. Mean IgE was increased in group 1 but both groups otherwise shared a pattern of increased IgG1, decreased IgG2/4, and low-normal IgA. Lymphocyte subsets were skewed, with an increased percentage of CD4 and CD19 and decreased CD8 and natural killer cells. Gastroesophageal reflux, esophagitis, subtle enteropathy, and constipation were frequent in both groups. Of 55 exclusively breast-fed infants, 44 sensitized before weaning. Twenty-one of the mothers suffered from autoimmunity. CONCLUSIONS: There appears to be a recognizable pattern of immune deviation and minor enteropathy in children with multiple food allergy, irrespective of the speed of reactions. Disturbed gut motility is particularly common, as is a maternal history of autoimmunity.