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The diagnosis of celiac disease is confirmed by a characteristic abnormal appearance of the small intestine under the microscope. Flattening of the normal finger like projections called villi accompanied by signs of inflammation is taken to indicate damage or injury from the storage protein gluten in wheat and similar proteins in barley and rye. The small intestine biopsy has became the gold standard for establishing the diagnosis of Celiac disease or gluten sensitive enteropathy. Before 1960 gluten withdrawal followed by improvement and subsequent worsening upon rechallenge was the diagnostic criteria.
Early in the 1960’s through the 1970’s the small intestine was biopsied by having people swallow a small metal capsule that was attached to a suction tube. This was used to suction up tissue into the capsule before guillotining off some tissue once the capsule was confirmed to be in the small intestine by x-ray. Now the tissue is obtained by upper endoscopy, the passage of a lighted video scope through the mouth under sedation to the small intestine, where biopsies are obtained with cupped forceps.
Celiac disease biopsy: What does the pathologist look for under the microscope?
The small intestine normally has finger like projections called villi that give it a large surface area or contact area for absorption. The villi result in a shag carpet or terry cloth towel type appearance. Lining the outside surface of each villous are intestinal cells or enterocytes that secrete mucus and absorb fluids, nutrients, minerals like iron, and vitamins like B12. On the surface of the enterocytes are digestive enzymes like lactase that digest lactose or milk sugar. At the base of the villi are crypts or circular like collections of intestinal cells.
Celiac disease biopsy: What is villous atrophy?
Normally, villi are 3-5 times longer than the crypts are tall. However, intestinal injury can result in blunting, shortening (partial villous atrophy) or complete loss of the villi and flattening (villous atrophy) of the intestinal surface. The shag carpet will have bare spots or the terry cloth towel becomes like a tee shirt. The result is lack of absorption of nutrients and water resulting in weight loss, malnutrition, and diarrhea.
Celiac disease biopsy: What if the biopsy does not show atrophy or partial atrophy?
If the villi are at least 3 times as long as the crypts are tall then no flattening or blunting of the villi is present and celiac disease becomes more difficult for the pathologist to diagnose without the history or blood test results. However, an increased number of IEL’s (intra-epitheliel lymphocytes) in the setting of a positive specific blood test for celiac, symptoms and especially if supported by presence of DQ2 and/or DQ8 gene pattern, is highly suggestive of celiac disease. The difficulty comes when the blood tests for the specific tests are negative or not elevated but only the “non-specific” blood tests (anti-gliadin or AGA and anti-reticulin antibodies) are elevated. Also, some people with milder forms of celiac have no blood tests abnormal but have classic biopsy findings of celiac and are termed seronegative (blood test negative) celiacs.
Celiac disease biopsy: Can the biopsy be normal in celiac disease?
By definition, the biopsy has been considered the gold standard for diagnosing celiac. However, recent studies have shown that the biopsy can be normal in some people with celiac. How can this be? The pathologist reading the biopsy may interpret the biopsy as normal based on his or her bias about celiac disease, a failure to appreciate the significance of the presence of IEL’s, or misuse of the older standard of >40 IEL’s per 100. However, more importantly is the recent recognition that normal appearing biopsies may not be normal. Electron microscopy has revealed ultra-structural abnormalities in apparent normal biopsies of people confirmed to have celiac disease. Special stains, that include immune labeling of lymphocytes, have also confirmed increased numbers of certain types of specific lymphocytes in the villi of intestinal biopsies of people confirmed to have celiac. The bottom line is that a normal biopsy does not definitively exclude celiac disease or gluten sensitivity.
Celiac diasease biopsy: What are other possible causes of biopsy changes that mimic celiac disease?
Cow’s milk protein sensitive enteropathy (CMSE), viral or bacterial infections, medications (especially aspirin like arthritis medications e.g. ibuprofen etc), autoimmune enteropathy, Helicobacter pylori infection (the stomach ulcer bacteria), AIDs, common variable immunodeficiency, and lymphoma of the intestine are all possible causes of small intestine changes that may mimic celiac. However, if you have classic celiac type symptoms, a positive celiac specific antibody (anti-endomysial antibody or tissue transglutaminase antibody) and a positive response to a gluten free diet then celiac is the likely cause. The likelihood is further increased if you carry one or both of the two major genes associated with celiac disease, DQ2 and/or DQ8. Normalization of celiac specific blood tests and the biopsy after a gluten free diet confirms the diagnosis of celiac disease.
write by Martha