Celiac Disease: Summary

Celiac disease (CD) is a disorder of small bowel malabsorption. It is characterized by mucosal inflammation, villous atrophy, and crypt hyperplasia, which occur upon exposure to gluten, and clinical and histological improvement with withdrawal of gluten from the diet. CD— also referred to as celiac sprue, gluten-sensitive enteropathy, non-tropical sprue, in addition to a host of other names—is thought to result from the activation of both a cell-mediated (T-cell) and humoral (B-cell) immune response upon exposure to the glutens (prolamins and glutenins) of wheat, barley, rye, and oats, in a genetically susceptible person. Genetic susceptibility is suggested by a high concordance among monozygotic twins of close to 70 percent, and an association with certain type II human leukocyte antigens (HLA). HLA DQ2 is found in up to 95 percent of CD patients, while most of the remaining patients have HLA DQ8. However, there is only a 30 percent HLA concordance among siblings, suggesting that other genetic factors are also at play. More recent evidence suggests that the presence of auto-antibodies to a connective tissue element surrounding smooth muscle called endomysium is highly specific for CD. The target of this autoantibody is now known to be an enzyme called tissue transglutaminase (tTG). This enzyme may play a prominent role in the pathogenesis of CD by modifying gliadin, resulting in a greater proliferative response of gliadin specific T-cells, which contributes to mucosal inflammation and further B-cell activation. CD appears to represent a spectrum of clinical features and presentations. Although “classical” CD (i.e., fully developed gluten-induced villous atrophy and classical features of intestinal malabsorption) is most commonly described, it appears that most patients have atypical CD (i.e., fully developed gluten-induced villous atrophy found in the setting of another presentation such as iron deficiency, osteoporosis, short stature, or infertility) or silent CD (i.e., fully developed gluten-induced villous atrophy discovered in an asymptomatic patient by serologic screening or perhaps an endoscopy for another reason). Other authors describe a latent form of CD that is characterized by a previous diagnosis that responded to a gluten-free diet (GFD) and retained a normal mucosal histology upon later introduction of gluten. Latent CD can also represent patients with currently normal intestinal mucosa who will subsequently develop glutensensitive enteropathy. The true prevalence of CD is difficult to estimate because of the variable presentation of the disease, particularly since many patients can have little or no symptoms. With this limitation in mind, the prevalence of the disease is highest in Celtic populations where estimates of 1:300 to 1:122 have been described. The prevalence of CD in North America has been estimated to be 1:3000, but a recent American study found the prevalence among the general not-at-risk population to be 1:105, while the prevalence in at-risk groups such as first-degree relatives of CD patients was 1:22, suggesting that CD is greatly under diagnosed. CD can affect persons of many ethnic backgrounds, but appears to rarely affect persons of purely Chinese, Japanese, or AfroCaribbean decent. The diagnosis of CD in adults is classically made on the basis of clinical suspicion—that is, recognizing atypical presentations such as isolated iron deficiency, combined iron and folate deficiency, and osteoporosis—compatible with a duodenal biopsy while taking a gluten-containing diet, followed by clinical and histological improvement following commencement of a GFD. However, several serologic markers have become available that have altered the classic Evidence Report/Technology Assessment