Celiac Disease Biopsy Explained – Part II

In this article, additional details are provided regarding the appearance of the intestine under the microscope in celiac disease and gluten sensitivity. The terms intraepithelial lymphocytosis and crypt hyperplasia are defined and explained for those who want to know what doctors look for when a small bowel biopsy is recommended when evaluating possible celiac disease.

Celiac disease biopsy: what is crypt hyperplasia and intraepithelial lymphocytosis?

Crypts may enlarge (crypt hyperplasia) in response to an injury stimulus or a perceived threat of invasion of the body. White blood cells called lymphocytes are activated and sent from the crypt areas to the tips of the villi. This results in what is called intraepithelial lymphocytosis or an increase in intraepithelial lymphocytes (IEL). It is the hallmark of celiac disease and the first sign of gluten sensitivity. However, it is not specific for celiac disease or gluten sensitivity.

Celiac disease biopsy: What is considered a normal IEL count?

More than 30 years ago, the standard threshold for IEL was 40 per 100 enterocytes (or 8/20 enterocytes). More recently this standard has been lowered to 30 per 100 (6/20) although recently the literature has suggested the number should be as low as 25 per 100 (5/20). Other studies have reported that potential celiac disease should be suggested by an average greater than 9-12 lymphocytes per villous tip over 5 villi. Sometimes lymphocytes are difficult to see or count, so special stains are needed or indicated. These spots stain the particular type of lymphocyte that is activated in celiac disease, making it quite easy to see and count them. It can also be useful when a person has already restricted gluten in their diet or started a gluten-free diet before the biopsy.

Celiac disease biopsy: what does gluten sensitivity look like on biopsy?

Symptoms of gluten sensitivity may be present and improve with a gluten-free diet in people with normal blood tests and normal intestinal biopsies. If the celiac blood tests are negative or normal, the biopsy is usually normal. However, this is not always the case and some people with true celiac disease have a classic celiac biopsy with normal blood tests. Also, early celiac disease is characterized by more subtle changes on biopsy, and in this setting blood tests are usually negative. Also, some biopsies may look normal under the microscope, but with special stains or electron microscopy they are not normal and show signs of gluten sensitivity or injury.

These people may be early celiacs and are usually gluten sensitive. Therefore, we sometimes end up with a problem of semantics. Gluten sensitivity with normal blood tests and biopsies responding to a gluten-free diet is well recognized. However, a clear definition for this is not widely accepted. Some people labeled as gluten sensitive are people who have early celiac disease where there is not enough damage to their gut to cause high or positive blood tests and/or they do not have characteristic changes of damage due to gluten. to gluten on their small intestine biopsy. Others, especially those without DQ2 or DQ8, do not appear to be at significant risk for true celiac disease, but respond favorably to a gluten-free diet.

Celiac disease biopsy: Who needs a biopsy?

If you have any symptoms, family history, or risk factors for celiac disease, you should have a complete blood test AND a small bowel biopsy before starting a gluten-free diet. This will determine if you have specific blood tests and a characteristic diagnostic biopsy. Genetic testing for DQ2 and DQ8 can determine if you are a carrier of one of the main gene patterns present in more than 98% of people with celiac disease, but their presence does not confirm celiac disease (30-40% of people are carriers of one or both genes in the US) and their absence also does not exclude gluten sensitivity or a low risk of celiac disease.

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