Screening for celiac disease in children with type 1 diabetes: two views of the controversy.

Abstract

Celiac sprue is a chronic intestinal disorder caused by hypersensitivity to prolamins, the glutamine- and proline-rich gluten proteins contained in wheat, rye, and barley. Genetically predisposed subjects who ingest cereal proteins develop an inflammatory enteropathy characterized by proliferation of intraepithelial lymphocytes, crypt hyperplasia, and partial or complete atrophy of small intestinal villi. The inflammatory response is induced by cross-linking and transamidation of gluten peptides by tissue transglutaminase, an enzyme localized to the connective tissue (lamina propria or endomysium) underlying the epithelial cells of the small intestine. Posttranslational modification of gluten enhances its uptake by dendritic cells and its binding to HLA-DQ2 and DQ-8, which induce T-cell activation and cytokine release (1,2). The resulting inflammation is accompanied by development of circulating antibodies to transglutaminase and to the endomysium. Inflammatory denudation of the villous surface gives rise to malabsorption of foodstuffs, folate, fat-soluble vitamins, and iron. Young children with classical symptomatic celiac disease may present with diarrhea and growth failure, muscle wasting, hypotonia, pallor, edema, anemia, and in some cases, rickets. Older children and adults with classical celiac disease may have episodic diarrhea, steatorrhea, weight loss, and osteoporosis, and the risk of gastrointestinal malignancy is increased (3–7). However, many children and adults with celiac disease have nonclassical forms of the illness. So-called silent celiac disease refers to partial or complete villous atrophy in a seropositive patient who has no gastrointestinal or extra-intestinal complications. Subclinical celiac disease refers to villous atrophy in a seropositive patient who has extra-intestinal complications but few or no gastrointestinal complaints. Extra-intestinal maladies associated with celiac disease may include anovulation, infertility and miscarriage, neurologic disorders and epilepsy, and hepatocellular dysfunction. Studies in Western Europe, North America, and Australia indicate that the prevalence of celiac disease among children and adults with type 1 diabetes (mean 4.1%, …