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Intraepithelial Lymphocytosis - Causes, Diagnosis, and Treatment

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Intraepithelial lymphocytosis refers to a condition characterized by an increased number of lymphocytes within the epithelial layer of a tissue or organ.

Medically reviewed by

Dr. Abdul Aziz Khan

Published At November 24, 2023
Reviewed AtNovember 24, 2023


A medical professional knows that diagnosing patients can often be challenging. Diseases manifest in complex ways, and symptoms are not always clear-cut. One condition that can be perplexing is intraepithelial lymphocytosis, an influx of T lymphocytes in the epithelium. While frequently benign, intraepithelial lymphocytosis may indicate an underlying autoimmune or inflammatory condition and requires close monitoring.

People must understand intraepithelial lymphocytosis to properly assess and manage patients with this finding. What is it, what causes it, and how is it diagnosed and treated? This guide provides an overview of intraepithelial lymphocytosis to equip with the knowledge necessary to provide the best care for the patients. This article explores identifying intraepithelial lymphocytosis, possibly associated conditions, recommendations for further testing, and treatment options based on diagnosis.

What Is Intraepithelial Lymphocytosis?

Intraepithelial lymphocytosis refers to an increased number of lymphocytes, a type of white blood cell, in the lining of the esophagus, stomach, or intestines. This condition is usually detected during an upper endoscopy, where a tiny camera examines the upper digestive tract.

The average number of lymphocytes in the epithelial lining is typically five per 100 epithelial cells. A finding of >30 lymphocytes per 100 epithelial cells is considered intraepithelial lymphocytosis. This lymphocyte increase is usually a reaction to inflammation or damage in the area. Potential causes include:

  1. Celiac Disease: Gluten triggers the autoimmune disease of celiac disease. During an immune response, the small intestine lining is attacked.

  2. Helicobacter Pylori (H. pylori) Infection: A bacterial infection that can inflame the stomach and duodenum.

  3. Medications: Nonsteroidal anti-inflammatory drugs (NSAIDs) can irritate the stomach lining.

  4. Reflux Esophagitis: Stomach acid flows back into the esophagus, causing inflammation.

To determine the underlying cause, a physician may order further testing such as blood tests, stool tests, or biopsies of the affected area. Once the cause is identified, treatment such as a gluten-free diet, antibiotics, acid suppressants, or discontinuing medications may help reduce inflammation and ease symptoms. Intraepithelial lymphocytosis is often reversible with proper diagnosis and treatment of the underlying condition. Ongoing monitoring with repeat endoscopies may be needed to ensure complete healing and remission.

What Are the Common Causes of Intraepithelial Lymphocytosis?

Intraepithelial lymphocytosis, or an increased number of lymphocytes in the epithelium of the gut, has several possible causes.

  • Celiac Disease: Celiac disease is a common cause of intraepithelial lymphocytosis. The immune system in celiac disease reacts to gluten, wheat, barley, and rye protein. This immune reaction causes inflammation and damage to the small intestine's lining. Cutting gluten from the diet can help resolve symptoms and heal intestinal damage.

  • Infection: Certain infections, including those caused by Giardia lamblia, Cryptosporidium, and other parasites, can lead to intraepithelial lymphocytosis. These infections irritate the gut lining, triggering an immune response and increased lymphocytes. Antibiotic or anti-parasitic treatment may be needed to eliminate the disease and allow the gut lining to heal.

  • Non-Celiac Gluten Sensitivity: Sometimes gluten triggers an immune reaction even without celiac disease. This is known as non-celiac gluten sensitivity. Removing gluten from the diet can help improve symptoms like diarrhea, abdominal pain, bloating, and fatigue and may reduce intraepithelial lymphocytosis.

  • Autoimmune Enteropathy: Rare autoimmune disorders like autoimmune enteropathy, in which the immune system mistakenly attacks cells in the gut, can also cause intraepithelial lymphocytosis. Steroids or other immunosuppressants may help control inflammation and moderate symptoms.

How to Diagnose Intraepithelial Lymphocytosis?

To diagnose intraepithelial lymphocytosis, several tests may need to be performed.

  • Blood Testing: A complete blood count (CBC) measures the levels of red and white blood cells and platelets in the blood. The WBC (white blood cell) count may be elevated for intraepithelial lymphocytosis, indicating excess lymphocytes. Additional blood tests like a peripheral blood smear may be done to examine the blood cells under a microscope to determine if abnormal lymphocytes are present.

  • Biopsy: A tissue biopsy from the affected organ, such as the intestines or stomach, may need to be obtained. During an endoscopy procedure, a gastroenterologist will remove a small tissue sample to be examined. A pathologist then analyzes the sample to check for increased lymphocytes in the organ's epithelial tissue. If higher than normal levels are detected, intraepithelial lymphocytosis can be diagnosed.

  • Imaging Scans: People may undergo imaging tests like (CT and MRI scans) to check for any visible changes or abnormalities in the organs. These scans provide detailed images that can detect the thickening of organ walls or other structural changes that may indicate intraepithelial lymphocytosis.

  • Celiac Disease Testing: As celiac disease is a possible underlying cause of intraepithelial lymphocytosis, people may be tested for this autoimmune disorder. Blood tests check for specific antibodies like tissue transglutaminase (TTG) IgA and endomysial antibody (EMA) IgA. An endoscopy with duodenal biopsies may also be done to check for damage to the small intestine's lining from celiac disease. If testing is positive, following a gluten-free diet may help improve symptoms from intraepithelial lymphocytosis.

What Are the Treatment Options for Intraepithelial Lymphocytosis?

Once intraepithelial lymphocytosis has been diagnosed, the next step is determining an effective treatment plan. Many options are available depending on the severity of the condition and overall health.

  • Corticosteroids: Corticosteroids can help reduce inflammation in the intestines. They are often a first-line treatment for intraepithelial lymphocytosis. Steroids decrease the body's immune response and relieve chronic symptoms such as abdominal pain, diarrhea, and weight loss. However, long-term steroid use can cause side effects such as increased appetite, insomnia, mood changes, and high blood pressure.

  • Immunosuppressants: Immunosuppressant drugs may be prescribed to regulate an overactive immune system for moderate to severe intraepithelial lymphocytosis. Azathioprine and 6-Mercaptopurine are commonly used. These medications can take several months before becoming fully effective but often allow for lower steroid doses. Patients must be monitored for adverse effects such as nausea, fatigue, and increased infection risk.

  • Biologic Therapies: Newer biological therapies that target specific parts of the immune system may be options if other treatments have not provided relief. Infliximab, Adalimumab, and Vedolizumab are biologics used to treat intraepithelial lymphocytosis. A few weeks or months after using them, symptoms may improve. They are administered by injection or by infusion. Risks include allergic reactions, especially for the initial infusions. Close monitoring is needed.

  • Diet and Nutrition: Dietary changes may help complement medical treatment. A diet low in fiber, lactose, and irritating foods can reduce symptom discomfort. Intake of daily multivitamins and mineral supplements can help prevent nutritional deficiencies. Probiotics and prebiotics may aid digestion and support gut health. Staying hydrated and getting enough rest is also important for overall wellness.

Intraepithelial lymphocytosis can be managed well with time and the right combination of treatments. Ongoing follow-up with the doctor is needed to monitor disease activity and adjust therapy. Be sure to report any severe or persistent symptoms right away.

How Is Living With Intraepithelial Lymphocytosis?

  • Tips for Management: Living with intraepithelial lymphocytosis requires diligent management and care. To minimize discomfort and health impacts, there are several steps you can take:

  • Follow Up With The Doctor: Regular follow-ups with the doctor must be scheduled, especially in the months after diagnosis. The doctor may want to monitor the condition to determine whether it resolves independently or if treatment is needed. Report any worsening or new symptoms right away.

  • Manage Diet and Lifestyle: Healthy lifestyle changes can be made to support one’s health. Follow an anti-inflammatory diet low in gluten, dairy, and sugar. Stay hydrated, get plenty of rest, exercise regularly, and avoid alcohol and tobacco products. Manage stress through mindfulness practices like yoga or meditation. These steps can help reduce inflammation and support one’s immune system.

  • Consider Supplements or Medications: Depending on the symptoms and health needs, the doctor may recommend certain supplements or medications. Common options for intraepithelial lymphocytosis include:

    • Probiotics: To improve gut health and immunity.

    • Zinc: To support immune function.

    • Glutamine: An amino acid that helps maintain the health of the gastrointestinal tract lining.

    • Low-Dose Naltrexone: An immune-modulating medication that may help reduce inflammation.

  • Monitor for Complications: Be alert for potential complications, including malnutrition, fatigue, and a higher risk of gastrointestinal issues. Report any severe or persistent symptoms to the doctor right away. To avoid long-term health problems, diagnosing and treating complications early is essential.

  • With close follow-up, lifestyle changes, and the possible use of supplements or medications, the outlook for intraepithelial lymphocytosis can be good. Staying proactive about managing one’s health will help get one’s condition under control and minimize the risk of complications. Be patient through the process, as complete recovery or remission can take weeks, months, or longer for some individuals.


To sum up, intraepithelial lymphocytosis is challenging to diagnose and treat. However, with an accurate understanding of the causes, symptoms, and treatment options, people can work with their doctor to develop an effective plan. While IEL may be frustrating, the good news is that symptoms are minor or resolve over time for many. Staying informed, following recommendations, and maintaining a healthy lifestyle are the keys to coping with IEL. Although intraepithelial lymphocytosis is still not fully understood, researchers continue to make progress in developing new therapies and management strategies. People can achieve remission and return to living well with patience and perseverance.

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Dr. Abdul Aziz Khan
Dr. Abdul Aziz Khan

Medical oncology


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