The diagnosis and treatment of celiac disease

Abstract

Background: Celiac disease is an inflammatory disease of, the small intestine with a prevalence of roughly 0.5%-1%. Its symptoms arise in response to gluten consumption by genetically predisposed persons (HLA-DQ2/8). The autoantigen tissue transglutaminase (TG2) plays an important role in the pathogenesis of celiac disease.

Method: Selective review of pertinent literature, including guidelines from Germany and abroad.

Results: Celiac disease can present at any age with gastrointestinal or extraintestinal manifestations (e.g., malabsorption or Duhring's dermatitis herpetiformis); it can also be found in association with other (auto-)immune diseases, such as type 1 diabetes. Most cases are oligosymptomatic. The wide differential diagnosis includes food intolerances, intestinal infections, and irritable bowel syndrome, among other conditions. The definitive diagnosis requires the demonstration of celiac disease-specific autoantibody to TG2 (endomysium), which is over 90% sensitive and far over 90% specific, and the characteristic histologic lesions of the small-bowel mucosa and remission on a gluten-free diet.

Conclusion: An understanding of celiac disease ought to inform everyday clinical practice in all medical disciplines, because this is a common condition with diverse manifestations that can be effectively diagnosed and easily treated for the prevention of both acute and long-term complications. Patients should follow a strictly gluten-free diet for life.

Figure 1

The pathogenesis of celiac disease. Gluten peptides are taken up across the intestinal epithelium, deamidated through the activity of tissue transglutaminase (TG2), and presented in the lamina propria by dendritic cells (among others), thereby activating gluten-specific cytotoxic T cells and T helper cells. IL-15 formed in intestinal epithelial and dendritic cells stimulates intraepithelial lymphocytes. Other cytokines of the typical immune reaction of celiac disease include, for example, IFN-?, TNF-a, IL-8, IL-18, and IL-21 (modified from 8). Yellow lettering is used for processes, white lettering for cells and proteins. MMP, matrix metalloproteinase.

Figure 2

The mucosal lesions of celiac disease (Marsh–Oberhuber classification): the histologic changes of the intestinal mucosa consist of lymphocytic proliferation in the epithelium and the lamina propria, crypt hyperplasia, and lower height of the villi. A type 2 or type 3 lesion is required for the diagnosis of celiac disease. Modified from (e16)

Figure 3

Decision flowchart for the diagnostic evaluation of celiac disease (modified from 22): the diagnostic features that are confirmatory of celiac disease are shown in red, while those that rule it out are shown in brown. In latent celiac disease, it is important to demonstrate HLA-DQ2/8 positivity and to confirm or exclude the diagnosis both serologically and histologically while the patient continues to consume gluten (dotted arrows). The ESPGHAN criteria enabling the diagnosis of celiac disease without duodenal biopsy in children and adolescents are shown in light blue. Note: in rare cases (e.g., IgA deficiency), the typical antibodies or HLA-DQ2/8 may not be detectable in a patient with celiac disease. It follows that, whenever the clinical manifestations put celiac disease in the differential diagnosis, biopsy is indicated. EMA, anti-endomysium antibodies; GI, gastrointestinal tract