Celiac-associated pancreatic disease.

Abstract

Pancreatic disease may be caused by or co-exist with celiac disease. In this setting, endocrine and exocrine changes may occur. As a result, superimposed, severe clinical changes with marked nutritional alteration may result. Importantly, however, in some, endocrine and exocrine pancreatic function may be improved with a gluten-free diet. Early studies from Europe and the Americas have shown that celiac disease patients have an increased prevalence rate of type 1 diabetes mellitus [1-4]. In part, this relationship was possibly due to sharing of the human leukocyte antigen alleles, DR3, and by linkage disequilibrium, DQ2 [5]. Besides this hypothesized common “immune-mediated” etiopathogenesis, some celiacs with pancreatic disease likely have developed diabetic changes secondarily due to severe exocrine pancreatic failure, in part, related to celiac-induced protein malnutrition. To further evaluate the prevalence rate of type 1 diabetes in celiac disease, prospective studies using an initial screening IgA tissue transglutaminase antibody assay (tTG) were done at our center in children and adolescents with type 1 diabetes mellitus [6]. A total of 125 male and 108 female patients were evaluated from an established pediatric diabetes clinic. Of these, 15 male and 11 female patients had elevated tTG titers, of whom 19 were also positive for endomysial antibodies. Among these cases, 1 was already known to have celiac disease. Small intestinal biopsies were done in the other 18 children positive for both antibodies. In all, histopathological changes consistent with celiac disease were detected, ranging from increased numbers of intraepithelial lymphocytes to severe crypt hyperplastic villous atrophy (i.e., so-called Marsh 3 lesion). Studies also suggested that serial tTG titers in insulindependent diabetic children might play a useful clinical role in monitoring compliance to a gluten-free diet, possibly of value since close monitoring of compliance of children to a glutenfree diet may be exceedingly diffi cult. In this study, over 40% of diabetic children were asymptomatic, and yet, prospective serological screening facilitated selection for small intestinal biopsy evaluation. Overall, 7.7% of this entire pediatric patient population proved to have typical biopsy features of celiac disease. Remarkably, this rate was confi rmed in a more recent European study, published almost a decade later, showing tTG positivity in 8.6% of diabetic children and adolescents, many again asymptomatic or having non-specifi c or mild gastrointestinal symptoms [7].