Thousands of people are undergoing endoscopic exams daily without having tissue samples obtained. Sadly, though their exams may visually appear normal, under the microscope there are often microscopic findings that explain the symptoms that will respond to directed therapy. The gut is lined with superficial cells that contain a few immune cells that release chemical mediators that attract other cells to the area and fight off foreign invaders. Below is a table of normal values for various cells in the digestive tract lining.
Lymphocytes, eosinophils and mast cells are the immune cells that are normally present in small numbers in the surface cells of the gastrointestinal tract. A few lymphocytes are present in the tips of the surface cells that are a type of epithelial cell. These lymphocytes act as the body’s scouts. They survey the barrier of the gut to the inside of the body, looking for signs of potential invading infectious agents. Once an attack is perceived, they signal reinforcements to join them on the front lines.
When persistent increased numbers of lymphocytes are present in the surface cells, a chronic inflammatory condition of the gut exists. In the duodenum, autoimmune reaction to gluten in genetically susceptible individuals is a common but frequently missed cause of chronic inflammation known more commonly as celiac disease or Sprue.
Eosinophils and mast cells are types of immune cells involved in allergy reactions in the body. They are less commonly present in the gastrointestinal lining except when there are parasites, food allergies, or chronic inflammatory bowel diseases such as Crohn’s disease or ulcerative colitis. Eosinophilic gastrointestinal disorders are less common and a newly recognized condition, mastocytic enterocolitis, is diagnosed when excess mast cells are present in the small bowel and colon. However, mast cells may be difficult to see on biopsies without a special stain for tryptase, an enzyme present in mast cells that are immunologically activated.
The esophagus normally contains no eosinophils. The two exceptions gastroesophageal acid reflux in which small numbers, up to 6-7 usually and no more than 10-12 per high power field (40X magnification) are found in the lower esophagus only not in the mid or upper esophagus. Allergic eosinophilic esophagitis is diagnosed when 15 or more eosinophils per high power field are found in more than two fields or more than 20 to 24 per high power field in one field are seen or lesser numbers are present in the upper esophagus. Mast cells that are activated have also been found associated with allergic eosinophilic esophagitis and their presence supports allergic esophagitis over reflux as the cause of the increase eosinophils though it is believed some people have both conditions coexisting.
In the stomach and small intestine more than 10 eosinophils per high power field defines eosinophilic gastroenteritis. In the small intestine and colon more than 20 mast cells per high power field found in association with otherwise unexplained diarrhea is now termed mastocytic enterocolitis. This newly recognized and described entity is previously unrecognized cause of diarrhea in some patients diagnosed with irritable bowel syndrome who may have been told they have a normal colon exam though no biopsies were done. Similarly, more than 20 lymphocytes per 100 epithelial cells in the colon are found in lymphocytic colitis, another form of microscopic inflammation of the intestine resulting in diarrhea that may be inappropriately diagnosed as IBS.
In many of these patients, gluten sensitivity is to blame and the lymphocytic colitis is felt to represent a colonic form of celiac disease. In celiac disease, 30 or more lymphocytes in the tips of the villi per 100 epithelial cells is the earliest sign of gluten injury occurring before the villi become flattened or blunted. This finding may noted before the specific blood tests, anti-endomysial (EMA) and anti-tissue transglutaminase (tTG) antibodies appear in the blood even though the intestine is damaged enough to result in nutrient malabsorption and diarrhea. Anti-gliadin antibodies are often present however when significant intra-epithelial lymphocytosis is present along with symptoms that respond to gluten free diet. Lesser degrees of intra-epithelial lymphocytosis have been proposed as highly suggestive of early celiac disease and or gluten sensitivity, in the range of 20-25 per 100 epithelial cells.
In the colon, the presence of eosinophils is considered one of the earliest findings of chronic inflammatory bowel disease. In the right colon more than 20 eosinophils per high power field and in the left colon greater than 20 per high power field is considered abnormal and suggests eosinophilic colitis, chronic inflammatory bowel disease or a parasitic infection.
Eosinophils and mast cells release chemicals that irritate the bowel, increase permeability (cause leaky gut), increase contractions of the gut, increase intestinal secretions and heighten pain. Both cells are related to allergies including food allergies. It is therefore not difficult to conceive of a link to adverse food reactions in the development of intestinal irritation.
The important point to be aware of if you have gastrointestinal symptoms and are undergoing or have undergone an endoscopic examination is that a normal appearing intestinal lining does not exclude the presence of damage or irritation sufficient to cause symptoms of pain, bloating, gas, and diarrhea nor exclude impaired digestion and absorption.
Only through obtaining tissue samples that are examined under the microscope can abnormal types and number of inflammatory cells be identified. It is through biopsies of normal appearing intestinal lining that the correct diagnosis of various microscopic forms of gastrointestinal inflammatory diseases is confirmed. So, if you are preparing to undergo an endoscopic exam, I encourage you to insist that your doctor perform biopsies even they believe your exam looks normal. Based on the information I have reviewed above, a normal exam should be tip off that one of these microscopic conditions might be to blame for your symptoms.
References:
Al-Haddad S, and Ridell RH. “The role of eosinophils in inflammatory bowel disease.” Gut 2005; 54:1674-1675.
Guilarte M et al. “Diarrhoea-predominant IBS patients show mast cell activation and hyperplasia in the jejunum.” Gut 2007; 56:203-209.
Jakarte S et al. “Mastocytic enterocolitis. “Increased mucosal mast cells in chronic intractable diarrhea.” Arch Pathol Lab Med. 2006; 130:362-367.
Kirsch R et al. “Activated mucosal mast cells differentiate eosinophilic (allergic) esophagitis from gastroesophageal reflux disease.” Journal of Pediatric Gastroenterology and Nutrition 2007; 44: 20-26.
Liacouras CA. “Eosinophilic gastrointestinal disorders.” Practical Gastroenterology March 2007. 53-67.
Rubio CA et al. “Lymphocytic esophagitis: a histologic subset of chronic esophagitis.” Am J Clin Pathol. 2006; 125(3): 432-437.
Yousef MM et al. “Duodenal intraepithelial lymphocytes in disorders of the esophagus and stomach.” Clinical Gastroenterology and Hepatology 2006; 4:631-634.
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