Intraepithelial lymphocytosis is a complex immunological phenomenon. It commonly affects the gastrointestinal tract, where damage to the lining of tissue causes the number of lymphocytes (a type of white blood cell) in the area to increase.

Lymphocytosis refers to a high lymphocyte count. Lymphocytes play a crucial role in immune system function, protecting against germs, foreign substances, and abnormal cells. When lymphocyte numbers increase, it usually indicates the body is fighting an illness or another inflammatory condition.

Experts link intraepithelial lymphocytosis to celiac disease, an autoimmune disorder that gluten ingestion triggers. However, it can also occur in other gastrointestinal disorders, such as inflammatory bowel disease and microscopic colitis.

This article examines intraepithelial lymphocytosis, its causes, diagnosis, and treatment.

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Intraepithelial lymphocytosis occurs when the number of lymphocytes increases within the epithelial layer of different tissues and organs in the body. Lymphocytes are white blood cells supporting the immune system’s defense against infections and diseases.

It is a histological finding, meaning scientists only know a person has intraepithelial lymphocytosis after viewing the affected tissue sample under a microscope.

In normal circumstances, a small number of lymphocytes can be found within the epithelial layer, acting as a type of surveillance for the body’s immune system. However, in cases of intraepithelial lymphocytosis, there is an excessive accumulation of lymphocytes, which usually indicates an abnormal immune response or underlying disease.

Also, increasing lymphocytes in the epithelial layer can significantly affect tissue function and homeostasis (a healthy and balanced internal state).

Experts have studied intraepithelial lymphocytosis extensively in the gastrointestinal tract, where they associated it with various conditions, including celiac disease, a chronic autoimmune disorder.

How does it affect the duodenum?

Intraepithelial lymphocytosis can occur in the epithelial layer of the duodenal mucosa. The duodenum is the first part of the small intestine, responsible for receiving partially digested food from the stomach and facilitating further digestion and nutrient absorption.

Symptoms of duodenal intraepithelial lymphocytosis can vary depending on the underlying condition and individual factors. People may sometimes experience the following:

  • abdominal pain
  • bloating
  • diarrhea
  • weight loss
  • nutrient deficiency

These symptoms may be chronic or intermittent, and their severity can vary.

While doctors do not fully understand the exact mechanisms, several potential triggers can lead to an infiltration of lymphocytes into the duodenal epithelial layer.

Besides celiac disease, these may include:

  • refractory celiac disease, a condition where a gluten-free diet does not ease symptoms
  • other autoimmune conditions that affect the gastrointestinal tract
  • infections, such as Helicobacter pylori (H. pylori), which can lead to duodenal ulcers
  • drug-induced reactions
  • environmental triggers, such as exposure to allergens or toxins
  • a genetic predisposition

Diagnosing intraepithelial lymphocytosis involves a thorough evaluation by a doctor or specialist gastroenterologist. They may conduct a physical examination to assess the person’s overall health and identify any signs or symptoms that relate to intraepithelial lymphocytosis.

Doctors can order blood tests to assess various markers and evaluate potential underlying causes. These tests can help determine if there are any of the following aspects:

  • specific immune abnormalities
  • nutritional deficiencies
  • signs of inflammation or infection

Depending on these findings, they may order an endoscopy with biopsies. A doctor inserts a flexible tube with a camera (endoscope) during this procedure. An upper endoscopy (through the mouth) is what doctors use to visualize the duodenum. A lower endoscopy or colonoscopy (through the anus) assesses the lower intestine.

The doctor can then take biopsy samples from the intestine’s lining and analyze them under a microscope to confirm a finding of intraepithelial lymphocytosis. It can also help rule out other conditions.

The treatment approach for intraepithelial lymphocytosis depends on the underlying cause and the severity of the symptoms.

In cases where intraepithelial lymphocytosis associates with conditions such as celiac disease or food allergies, adopting a strict gluten-free or allergen-free diet can help alleviate symptoms and reduce the inflammation in the duodenum.

A registered dietitian can guide appropriate dietary modifications and ensure proper nutrient intake, but this may not work for everyone.

Doctors may also use antibiotics to treat underlying infections with H. pylori or other bacteria. Other medications can help manage symptoms such as abdominal pain, diarrhea, or malabsorption.

In some cases, if doctors do not identify or treat the underlying cause, intraepithelial lymphocytosis may persist and potentially contribute to ongoing inflammation and damage to the affected tissue.

Below are some common questions on the topic:

What is focal intraepithelial lymphocytosis?

Focal intraepithelial lymphocytosis is a specific form of the condition featuring increased lymphocytes in a localized area of the epithelium.

Doctors may associate it with conditions or diseases such as small intestinal bacterial overgrowth (SIBO), H. pylori infection, or celiac disease.

Does celiac disease cause lymphocytosis?

Yes, celiac disease can cause lymphocytosis. In celiac disease, the immune system reacts to gluten, leading to inflammation and damage to the small intestine’s lining.

What is the outlook?

The outlook for intraepithelial lymphocytosis depends on what is causing it and the person’s general health. People may wish to speak with a gastroenterologist or a doctor to help them manage any underlying disease — for example, inflammatory bowel disease.

Intraepithelial lymphocytosis is a condition featuring an increased number of lymphocytes in the epithelium, most commonly in the duodenum. Experts associate it with celiac disease, H. pylori infection, and certain drug reactions.

Doctors diagnose intraepithelial lymphocytosis through tissue biopsy and histopathological examination (using a microscope to observe tissue) in a laboratory.

While doctors do not fully understand the exact cause of this condition, they believe that it relates to immune system dysregulation and inflammation. Therefore, treatment will address the underlying cause, such as implementing a gluten-free diet for celiac disease, eradicating H. pylori infection, or discontinuing medications triggering the immune response.