Intraepithelial lymphocytosis (IEL) is a finding observed under a microscope, indicating an increased number of lymphocytes within the epithelial lining of various organs. Lymphocytes are a type of white blood cell that plays a role in the body’s immune system, helping to defend against infections and diseases. This finding itself is not a specific disease but rather a sign that the immune system is responding to some form of irritation or abnormality within the tissue. It often prompts further investigation to determine the underlying cause.
What is Intraepithelial Lymphocytosis?
Intraepithelial lymphocytosis refers to an elevated count of lymphocytes within the epithelial layer of tissues. While often found in the gastrointestinal tract, especially the small intestine, these lymphocytes can also appear in the stomach, colon, skin, and genital tract. In a healthy small intestine, fewer than 5-10 lymphocytes per 100 epithelial cells are typical. An increase to 20-25 lymphocytes per 100 epithelial cells or more is considered intraepithelial lymphocytosis.
These lymphocytes, particularly T-cells, are components of the gut-associated lymphoid tissue (GALT) and are involved in immune surveillance. They patrol the space between intestinal epithelial cells, forming a first line of defense against pathogens and maintaining the intestinal barrier. When their numbers increase, it suggests an immune response or inflammation is occurring in that tissue. This elevated lymphocyte activity can affect the normal function of the tissue.
Conditions Linked to Intraepithelial Lymphocytosis
Intraepithelial lymphocytosis frequently points to an underlying medical condition, with celiac disease being one of the most common associations. Celiac disease is an autoimmune disorder where consuming gluten triggers an immune response that damages the small intestine, leading to an increase in intraepithelial lymphocytes. In individuals with celiac disease, the small intestine may show increased intraepithelial lymphocytes along with villous atrophy, which is a flattening of the small intestinal lining.
Beyond celiac disease, other conditions can also lead to intraepithelial lymphocytosis. The use of certain medications, such as non-steroidal anti-inflammatory drugs (NSAIDs) or proton pump inhibitors (PPIs), has been linked to this finding. Infections, including Helicobacter pylori in the stomach, can also cause an increase in intraepithelial lymphocytes.
Inflammatory bowel diseases (IBD), such as Crohn’s disease and ulcerative colitis, are also associated with increased lymphocytes in the intestinal lining. Other potential causes include:
Small intestinal bacterial overgrowth (SIBO)
Tropical sprue
Allergies to certain foods like dairy or soy
Autoimmune enteropathy
Graft-versus-host disease
While intraepithelial lymphocytosis itself is not a diagnosis, its presence indicates the need for further evaluation to identify the underlying cause.
How Intraepithelial Lymphocytosis is Identified and Addressed
The identification of intraepithelial lymphocytosis typically begins with a tissue biopsy, often performed during an endoscopy. During an upper endoscopy, a flexible tube with a camera is inserted through the mouth to visualize and take small tissue samples from the duodenum, the first part of the small intestine. For assessing the lower intestine, a colonoscopy may be performed. These tissue samples are then examined under a microscope by a pathologist to count the number of lymphocytes within the epithelial layer.
Once intraepithelial lymphocytosis is confirmed, the next step involves a thorough evaluation to pinpoint the underlying cause. This may include various blood tests to check for specific immune abnormalities, nutritional deficiencies, or signs of inflammation or infection. For instance, blood tests for celiac disease antibodies are often conducted. Depending on the suspected cause, stool tests or imaging studies might also be ordered.
Management of intraepithelial lymphocytosis focuses on treating the identified underlying condition. For example, if celiac disease is diagnosed, a strict gluten-free diet is the primary treatment. If H. pylori infection is found, antibiotics are used to eradicate the bacteria. In cases linked to medications, discontinuing the offending drug may resolve the issue. Addressing the root cause is important, as persistent intraepithelial lymphocytosis without treatment can contribute to ongoing tissue inflammation and damage.