Dr  Sampurna Roy  MD

Syn: Gluten sensitive enteropathy ; Gluten induced enteropathy ; Non-tropical sprue.

             
Coeliac disease is an immune-mediated enteropathy triggered by the ingestion of gluten-containing grains (including wheat, rye, and barley) in genetically susceptible persons. The disease is associated with HLA-DQ2 in 90 to 95 percent of cases and with HLA-DQ8 in 5 to 10 percent of cases and is self-perpetuating in the continued presence of gluten. It is the interplay between genes (both HLA and other types) and environment (i.e., gluten) that leads to the intestinal damage that is typical of the disease.
In about 10% patients, lymphocytic gastritis is present.

Coeliac disease is associated with conditions such as type I diabetes mellitus and autoimmune thyroid disease. A similar association has been proposed with other autoimmune conditions such as primary biliary cirrhosis and Sjogren's syndrome. The basis of this is unclear. A genetic mechanism has been postulated.

A number of neurological disorders have been described in association with coeliac disease, mainly as case reports, the most frequent being cerebellar dysfunction, epilepsy, and peripheral neuropathy. Malabsorption may lead to vitamin and trace element deficiencies. Therefore, patients who develop neurological dysfunction should be carefully screened for these.

 Visit: Normal histology of the small intestine for anatomic pathologists

HISTOLOGICAL FEATURES:
- The histological features are severe in the proximal part of the small intestine and gradually becomes less prominent  in the distal intestinal mucosa.
- Villous atrophy may be subtotal or partial, which is usually patchy or diffuse.
- Diffuse enteritis characterized by infiltration of lamina propria by lymphocytes and plasma cells. Scattered  polymorphs and eosinophils are also noted.
- The most reliable change of celiac disease is the number of intraepithelial lymphocytes per100 surface epithelial cells . More than 30 IELs per 100 epithelial cells is significant. (Normal range 10-30)
- The activated T-lymphocytes have large, folded nuclei.
- Untreated cases are characterized by flat mucosa & more than 50 IELs.
- Degeneration of enterocytes, increased enterocyte apoptosis, loss of basilar alignment of enterocyte nuclei and becomes stratified.
- Crypt hyperplasia characterized by elongated crypts, mitoses extend into upper third. 
- Anti-gliadin , anti-endomysial antibodies play an important role in supporting the diagnosis.
- A second biopsy should be performed 3 to 6 weeks after initiating gluten free diet.
- In the first biopsy the histopathologist describes the abnormalities and concludes the report as - "The features are consistent with Coeliac Disease".

According to the Marsh  classification :

Type 0 :  corresponds to normal mucous membrane, and

Type 1 :  the infiltrative type, is characterised by an increase in intraepithelial lymphocytes (IEL), which amount to more than 40 lymphocytes/100 enterocytes.

Type 2 :  has normal villous architecture, an increase in IEL numbers and crypt hyperplasia.

Type 3 :  the destructive type, is characterised by villous atrophy and may be divided into three sub-groups depending on the degree of the atrophy-mild, marked, and total (flat mucosa).

Combination of these histopathological findings, patient's history and clinical course may result in the definition of six "states" of celiac disease. Marsh' classification is helpful for an early diagnosis of the disease

A definitive diagnosis can be made after correlating the histological features with serological tests and clinical features . A repeat biopsy showing response to gluten free diet confirms the diagnosis.

Visit: An approach to evaluation of small intestinal biopsy

 Differential diagnosis :    Visit: Tropical Sprue

Focal severe villus abnormality is noted in common variable immune deficiency (plasma cells are absent) ;  Protein allergen other than gluten ; Some cases of tropical sprue ;  Crohn's disease (patchy infiltrate, fissure ulcer, microgranuloma, focal crypt destruction) ;  T-cell lymphoma ;  Chronic peptic duodenitis (usually in the first part of duodenum, no intraepithelial lymphocytosis) ;  Partial villous atrophy associated with dermatitis herpetiformis ; Injuries related to the use of drugs such as neomycin and triparanol ; Lymphocytic enterocolitis ; Stasis or blind-loop syndromes.

Visit:  Malabsorption syndrome ;Enteropathy-associated T-cell lymphoma

Malabsorption with small-intestinal mucosal injury resembling that of celiac disease also occurs in association with infectious agents, including protozoa and viruses. In all these disorders, blunting to near-total flattening of mucosal villi may be seen, but total villous atrophy like that caused by coeliac disease is less common and the injury is often more patchy. In addition, the other microscopical features of celiac disease , specially the increased number of intraepithelial lymphocytes are generally less prominent.