Definition

• An autoimmune disorder caused by an abnormal immune response to dietary gluten.

 Epidemiology

 • Common, affecting ~1% of the population.

Aetiology

 • Dietary gluten and related proteins.

Pathogenesis

• the culprit proteins are poorly digested by intestinal proteases.

• Intact peptides enter the lamina propria and are deamidated by tissue transglutaminase, rendering them negatively charged.

 • Negatively charged peptides bind more efficiently to human leucocyte antigen (HLA) receptors on antigen- presenting cells which are recognized by intestinal T- cells.

• Activated T- cells stimulate an immune reaction in the intestinal wall.

Presentation

 • Symptoms relating to the GI tract may be present such as weight loss, abdominal pain, and diarrhoea.

 • however, many patients are asymptomatic and only diagnosed during investigation of an iron deficiency anaemia.

 Serology

• Presence of serum IgA endomysial or transglutaminase antibodies is highly specific and sensitive for coeliac disease. Care must be taken in interpreting these results in patients who are IgA- deficient.

 Macroscopy

 • Blunting and flattening of villi may be visible under a dissecting microscope (and may be identified at endoscopy).

 Histopathology

• fully developed cases show increased intraepithelial lymphocytes (>20/ 100 epithelial cells), mainly at the tips of the villi, many lymphocytes and plasma cells in the lamina propria, villous atrophy, and crypt hyperplasia (fig. 1).

• Milder cases may only show increased intraepithelial lymphocytes without villous atrophy. this is termed lymphocytic duodenitis.

* Note that none of these changes are specific to coeliac disease; identical changes can be seen in a number of other conditions, e.g. drugs, tropical sprue. Biopsy findings must be interpreted in light of the clinical and serological picture.

 Prognosis

 • Strict adherence to a gluten- free diet leads to resolution of symptoms and normalization of histology, although architectural changes may take some time to normalize. Cases which do not respond to a gluten- free diet need to be carefully assessed for the development of a lymphoma.

• Increased risk of type 1 diabetes, autoimmune thyroid disease, dermatitis herpetiformis, oropharyngeal and oesophageal carcinomas, small bowel adenocarcinoma, and a rare, but highly aggressive, form of t- cell lymphoma known as enteropathy- associated t- cell lymphoma (EATL).

FIG1. (a) Normal duodenal mucosa. the villi have a normal height and shape, and there is no increase in intraepithelial lymphocytes. (b) Duodenal biopsy from a patient with gluten- sensitive enteropathy. the villi have completely disappeared and the surface epithelium contains many intraepithelial lymphocytes . reproduced with permission from Clinical Pathology (Oxford Core texts), Carton, James, Daly, richard, and ramani, Pramila, Oxford University Press (2006), p.154, figure 8.8.