In this article, further detail is provided regarding the appearance of the intestine under the microscope in celiac disease and gluten sensitivity. The terms intra-epithelial lymphocytosis and crypt hyperplasia are defined and explained for those wanting to know what doctors are looking for when a biopsy of the small intestine is recommended during the evaluation of possible celiac disease.
Celiac disease biopsy: What is crypt hyperplasia and intra-epithelial lymphocytosis?
The crypts can become enlarged (crypt hyperplasia) in response to stimulus of injury or perceived threat of invasion to the body. White blood cells called lymphocytes are activated and sent up from the crypt areas to the tips of the villi. This results in what is termed intra-epithelial lymphocytosis or increased intra-epithelial lymphocytes (IELs). This is the hallmark of celiac disease and the earliest sign of gluten sensitivity. It is not however specific for celiac disease or gluten sensitivity.
Celiac disease biopsy: What is considered a normal number of IELs?
Over 30 years ago the standard cutoff for IELs was 40 per 100 enterocytes (or 8/20 enterocytes). More recently that standard has been lowered to 30 per 100 (6/20) though recently the literature has suggested that the number should be as low as 25 per 100 (5/20). Other studies have reported potential celiac disease should be suggested by an average of greater than 9-12 lymphocytes per villous tip over 5 villi. Sometimes, the lymphocytes are hard to see or count so special stains are needed or indicated. These stains stain the particular type of lymphocyte that is activated in celiac disease allowing them to be seen and counted quite easily. This also may be helpful when someone has already restricted gluten in their diet or initiated a gluten free diet prior to the biopsy.
Celiac disease biopsy: What does gluten sensitivity look like on biopsy?
The symptoms of gluten sensitivity can be present and improve with gluten free diet in people with normal blood tests and normal intestinal biopsies. If celiac blood tests are negative or normal then the biopsy is usually normal. However, this is not always the case and some people with true celiac disease have a classic biopsy for celiac with normal blood tests. Moreover, early celiac disease is characterized by more subtle changes on biopsy and in this setting the blood tests are usually negative. Furthermore, some biopsies may look normal under the microscope but with special stains or electron microscopy are not normal and show signs of gluten sensitivity or injury.
These people may be early celiacs and are usually gluten sensitive. Therefore, we are sometimes left with a semantics problem. Gluten sensitivity with normal blood tests and biopsies that responds to a gluten free diet is well recognized. However, a clear-cut definition for this is not widely accepted. Some people labeled as gluten sensitive are people who have early celiac disease where not enough injury of their intestine has occurred to result in elevated or positive blood tests and/or they don’t have characteristic changes of injury from gluten on their small intestine biopsy. Others, particularly those without DQ2 or DQ8 appear not 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 suggestive symptoms, a family history or risk factors for celiac disease then you should undergo complete blood test screening AND a small bowel biopsy before initiating 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 carry either of the major gene patterns present in over 98% of people with celiac disease but their presence does not confirm celiac (30-40% of people carry one or both of the genes in the U.S.) nor does their absence exclude gluten sensitivity or a remote chance of celiac disease.