Gluten‐sensitive enteropathy (celiac disease)

Abstract

Gluten‐sensitive enteropathy (celiac disease—GSE) is induced by dietary wheat gliadin and related proteins in genetically susceptible individuals. Enzyme abnormalities and a lectin‐like gluten toxicity could be implicated in the pathogenesis of the disease, but most evidence suggests that the mucosal lesion of GSE represents an imraunologicaly mediated tissue injury triggered by gluten ingestion within the context of a particular assortment of major histocompatibility complex genes. The process leading to the mucosal damage is as yet still poorly understood, as well as the amino acid sequence(s) of gliadin and related proteins responsible for toxicity. Several in vitro models are available to test toxicity of gliadin amino acid sequences, pathogenesis of mucosal damage, and possible protective mechanisms, but definitive conclusions must rely on in vivo jejunal, and probably rectal, challenge studies in treated celiac patients. Animal models could contribute to the understanding of GSE pathogenesis. Symptomatic GSE affects approximately 1:1000 individuals in Europe, but this figure is likely to underestimate the real prevalence of the disease. In fact, many cases are asymptomatic, and they may be recognized only by means of large screening programs. Furthermore, it is now becoming clear that a condition of latent gluten sensitivity (preceliac disease) can exist in some apparently normal individuals, who present normal (or almost normal) jejunal histology while eating gluten. In some regions of Europe GSE is still presenting more often in the infantile age with classical gastrointestinal symptoms, but in other countries the clinical presentation is changing, coming closer to the adult type of the disease, and the age of onset of symptoms is shifting upward. Liver, joint, hematological, gynecological, and neurological symptoms are increasingly being recognized. A number of diseases have been found to be associated with GSE; among these are: IgA deficiency, IgA nephropathy, sarcoidosis, insulin‐dependent diabetes mellitus, and a range of other autoimmune diseases. The diagnosis of GSE is based on the finding of severe histological lesion of the jejunum while the patient is on a gluten‐containing diet, and on its disappearance once gluten is excluded from the diet. As far as therapy is concerned, a lifelong, strict gluten‐free diet is mandatory for GSE patients. Among other long‐term problems, an increased risk of intestinal lymphoma has been reported in those patients on a normal or even on a gluten‐poor diet.

Notes

To whom correspondence should be sent at: Dipartimento di Pediatria, II Facoltà di Medicina dell'Università di Napoli, via S. Pansini 5, 80131 Naples, Italy.